Pub Date : 2022-02-10DOI: 10.1186/s13053-022-00213-5
Kristin R Muessig, Jamilyn M Zepp, Erin Keast, Elizabeth E Shuster, Ana A Reyes, Briana Arnold, Chalinya Ingphakorn, Marian J Gilmore, Tia L Kauffman, Jessica Ezzell Hunter, Sarah Knerr, Heather S Feigelson, Katrina A B Goddard
Background: A critical step in access to genetic testing for hereditary cancer syndromes is referral for genetic counseling to assess personal and family risk. Individuals meeting testing guidelines have the greatest need to be evaluated. However, referrals to genetics are underutilized in US patients with hereditary cancer syndromes, especially within traditionally underserved populations, including racial and ethnic minorities, low-income, and non-English speaking patients.
Methods: We studied existing processes for referral to genetic evaluation and testing for hereditary cancer risk to identify areas of potential improvement in delivering these services, especially for traditionally underserved patients. We conducted a retrospective review of 820 referrals to the Kaiser Permanente Northwest (KPNW) genetics department containing diagnosis codes for hereditary cancer risk. We classified referrals as high- or low-quality based on whether sufficient information was provided to determine if patients met national practice guidelines for testing. Through chart abstraction, we also assessed consistency with practice guidelines, whether the referral resulted in a visit to the genetics department for evaluation, and clinical characteristics of patients receiving genetic testing.
Results: Most referrals (n = 514, 63%) contained sufficient information to assess the appropriateness of referral; of those, 92% met practice guidelines for genetic testing. Half of referred patients (50%) were not offered genetic evaluation; only 31% received genetic testing. We identified several barriers to receiving genetic evaluation and testing, the biggest barrier being completion of a family history form sent to patients following the referral. Those with a referral consistent with testing guidelines, were more likely to receive genetic testing than those without (39% vs. 29%, respectively; p = 0.0058). Traditionally underserved patients were underrepresented in those receiving genetic evaluation and testing relative to the overall adult KPNW population.
Conclusions: Process improvements are needed to increase access to genetic services to diagnose hereditary cancer syndromes prior to development of cancer.
{"title":"Retrospective assessment of barriers and access to genetic services for hereditary cancer syndromes in an integrated health care delivery system.","authors":"Kristin R Muessig, Jamilyn M Zepp, Erin Keast, Elizabeth E Shuster, Ana A Reyes, Briana Arnold, Chalinya Ingphakorn, Marian J Gilmore, Tia L Kauffman, Jessica Ezzell Hunter, Sarah Knerr, Heather S Feigelson, Katrina A B Goddard","doi":"10.1186/s13053-022-00213-5","DOIUrl":"https://doi.org/10.1186/s13053-022-00213-5","url":null,"abstract":"<p><strong>Background: </strong>A critical step in access to genetic testing for hereditary cancer syndromes is referral for genetic counseling to assess personal and family risk. Individuals meeting testing guidelines have the greatest need to be evaluated. However, referrals to genetics are underutilized in US patients with hereditary cancer syndromes, especially within traditionally underserved populations, including racial and ethnic minorities, low-income, and non-English speaking patients.</p><p><strong>Methods: </strong>We studied existing processes for referral to genetic evaluation and testing for hereditary cancer risk to identify areas of potential improvement in delivering these services, especially for traditionally underserved patients. We conducted a retrospective review of 820 referrals to the Kaiser Permanente Northwest (KPNW) genetics department containing diagnosis codes for hereditary cancer risk. We classified referrals as high- or low-quality based on whether sufficient information was provided to determine if patients met national practice guidelines for testing. Through chart abstraction, we also assessed consistency with practice guidelines, whether the referral resulted in a visit to the genetics department for evaluation, and clinical characteristics of patients receiving genetic testing.</p><p><strong>Results: </strong>Most referrals (n = 514, 63%) contained sufficient information to assess the appropriateness of referral; of those, 92% met practice guidelines for genetic testing. Half of referred patients (50%) were not offered genetic evaluation; only 31% received genetic testing. We identified several barriers to receiving genetic evaluation and testing, the biggest barrier being completion of a family history form sent to patients following the referral. Those with a referral consistent with testing guidelines, were more likely to receive genetic testing than those without (39% vs. 29%, respectively; p = 0.0058). Traditionally underserved patients were underrepresented in those receiving genetic evaluation and testing relative to the overall adult KPNW population.</p><p><strong>Conclusions: </strong>Process improvements are needed to increase access to genetic services to diagnose hereditary cancer syndromes prior to development of cancer.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39783946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-05DOI: 10.1186/s13053-022-00212-6
Nina Strømsvik, Pernilla Olsson, Berit Gravdehaug, Hilde Lurås, Ellen Schlichting, Kjersti Jørgensen, Teresia Wangensteen, Tone Vamre, Cecilie Heramb, Lovise Mæhle, Eli Marie Grindedal
Background: In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed "mainstreamed genetic testing". The aim of this study was to learn about patients' experience of this healthcare service.
Methods: Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data.
Results: The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing.
Conclusions: Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment.
{"title":"\"It was an important part of my treatment\": a qualitative study of Norwegian breast Cancer patients' experiences with mainstreamed genetic testing.","authors":"Nina Strømsvik, Pernilla Olsson, Berit Gravdehaug, Hilde Lurås, Ellen Schlichting, Kjersti Jørgensen, Teresia Wangensteen, Tone Vamre, Cecilie Heramb, Lovise Mæhle, Eli Marie Grindedal","doi":"10.1186/s13053-022-00212-6","DOIUrl":"https://doi.org/10.1186/s13053-022-00212-6","url":null,"abstract":"<p><strong>Background: </strong>In South-Eastern Norway, genetic testing for BRCA1 and BRCA2 is offered to breast cancer patients by their treating surgeon or oncologist. Genetic counselling from a geneticist or a genetic counsellor is offered only to those who test positive for a pathogenic variant or have a family history of cancer. This practice is termed \"mainstreamed genetic testing\". The aim of this study was to learn about patients' experience of this healthcare service.</p><p><strong>Methods: </strong>Qualitative in-depth interviews were conducted with 22 breast cancer patients who had been diagnosed during the first half of 2016 or 2017 at one regional and one university hospital and who had been offered testing by their treating physician. A six-phase thematic approach was used to analyse the data.</p><p><strong>Results: </strong>The participants had varied experiences of how and when testing was offered. Three main themes emerged from the analysis: 1. informational and communicational needs and challenges during a chaotic time, 2. the value of genetic testing and 3. the importance of standardised routines for mainstreamed genetic testing.</p><p><strong>Conclusions: </strong>Despite the shock of their diagnosis and the varying experiences they had in respect of how and when testing was offered, all of the participants emphasised that genetic testing had been an important part of their diagnosis and treatment. Our results indicate that there is a need for continuous collaboration between geneticists, surgeons, oncologists and laboratory specialists in order to establish simple and robust routines so as to ensure that all eligible breast cancer patients are offered testing at a point when the test result can have an impact on treatment.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39891917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-31DOI: 10.1186/s13053-022-00211-7
Kortbeek Koen, De Putter Robin, Naert Eline
We report the case of a breast cancer survivor, diagnosed with an underlying CHEK2 c.1100delC heterozygosity, who developed a papillary thyroid cancer 5 years later. A CHEK2 c.1100delC (likely) pathogenic variant is associated with an increased risk of breast, prostate and colorectal cancer and therefore risk-specific screening will be offered. Current national and international screening guidelines do not recommend routine screening for thyroid cancer. Hence, we reviewed the literature to explore the possible association between a CHEK2 mutation and thyroid cancer. A weak association was found between the various CHEK2 mutations and papillary thyroid cancer. The evidence for an association with CHEK2 c.1100delC in particular is the least robust. In conclusion, there is insufficient evidence to warrant systematic thyroid screening in CHEK2 carriers.
{"title":"CHEK2 mutations and papillary thyroid cancer: correlation or coincidence?","authors":"Kortbeek Koen, De Putter Robin, Naert Eline","doi":"10.1186/s13053-022-00211-7","DOIUrl":"10.1186/s13053-022-00211-7","url":null,"abstract":"<p><p>We report the case of a breast cancer survivor, diagnosed with an underlying CHEK2 c.1100delC heterozygosity, who developed a papillary thyroid cancer 5 years later. A CHEK2 c.1100delC (likely) pathogenic variant is associated with an increased risk of breast, prostate and colorectal cancer and therefore risk-specific screening will be offered. Current national and international screening guidelines do not recommend routine screening for thyroid cancer. Hence, we reviewed the literature to explore the possible association between a CHEK2 mutation and thyroid cancer. A weak association was found between the various CHEK2 mutations and papillary thyroid cancer. The evidence for an association with CHEK2 c.1100delC in particular is the least robust. In conclusion, there is insufficient evidence to warrant systematic thyroid screening in CHEK2 carriers.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-29DOI: 10.1186/s13053-022-00210-8
Bing-Rong Wang, Dong-Xia Chu, Mei-Yu Cheng, Yu Jin, Hao-Ge Luo, Na Li
The Hox transcript antisense intergenic RNA (HOTAIR) has been identified as a tumor gene, and its expression in HCC is significantly increased. HOTAIR is associated with the proliferation, invasion, metastasis and poor prognosis of HCC. In addition, HOTAIR can also regulate the expression and function of microRNA by recruiting the polycomb repressive complex 2 (PRC2) and competitive adsorption, thus promoting the occurrence and development of HCC. In this review, we discussed the two mechanisms of HOTAIR regulating miRNA through direct binding miRNA and indirect regulation, and emphasized the role of HOTAIR in HCC through miRNA, explained the regulatory pathway of HOTAIR-miRNA-mRNA and introduced the role of this pathway in HCC proliferation, drug resistance, invasion and metastasis.
{"title":"Progress of HOTAIR-microRNA in hepatocellular carcinoma.","authors":"Bing-Rong Wang, Dong-Xia Chu, Mei-Yu Cheng, Yu Jin, Hao-Ge Luo, Na Li","doi":"10.1186/s13053-022-00210-8","DOIUrl":"https://doi.org/10.1186/s13053-022-00210-8","url":null,"abstract":"<p><p>The Hox transcript antisense intergenic RNA (HOTAIR) has been identified as a tumor gene, and its expression in HCC is significantly increased. HOTAIR is associated with the proliferation, invasion, metastasis and poor prognosis of HCC. In addition, HOTAIR can also regulate the expression and function of microRNA by recruiting the polycomb repressive complex 2 (PRC2) and competitive adsorption, thus promoting the occurrence and development of HCC. In this review, we discussed the two mechanisms of HOTAIR regulating miRNA through direct binding miRNA and indirect regulation, and emphasized the role of HOTAIR in HCC through miRNA, explained the regulatory pathway of HOTAIR-miRNA-mRNA and introduced the role of this pathway in HCC proliferation, drug resistance, invasion and metastasis.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8800341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39869598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-21DOI: 10.1186/s13053-022-00209-1
Jelena Maksimenko, Arvīds Irmejs, Jānis Gardovskis
Background: Often young women affected with BRCA1/2 positive breast cancer have not finished or even not started their childbearing before the onset of the disease. The aim of our mini-review is to summarize state of art knowledge on pregnancy after breast cancer in BRCA1/2 carriers.
Methods: A broad review of the literature was conducted using MEDLINE (via PubMed) for relevant articles published. This review summarizes the impact of different cytotoxic agents on a fertility, fertility preservation, maternal and fetal prognosis after pregnancy in breast cancer survivors with BRCA1/2.
Conclusion: According to the existing literature evidence pregnancy after therapy for breast cancer in BRCA carriers is safe for the mother and offspring, but patients' needs, oncofertility counseling and fertility-sparing strategy should be carefully planned before starting the cytotoxic treatment.
{"title":"Pregnancy after breast cancer in BRCA1/2 mutation carriers.","authors":"Jelena Maksimenko, Arvīds Irmejs, Jānis Gardovskis","doi":"10.1186/s13053-022-00209-1","DOIUrl":"https://doi.org/10.1186/s13053-022-00209-1","url":null,"abstract":"<p><strong>Background: </strong>Often young women affected with BRCA1/2 positive breast cancer have not finished or even not started their childbearing before the onset of the disease. The aim of our mini-review is to summarize state of art knowledge on pregnancy after breast cancer in BRCA1/2 carriers.</p><p><strong>Methods: </strong>A broad review of the literature was conducted using MEDLINE (via PubMed) for relevant articles published. This review summarizes the impact of different cytotoxic agents on a fertility, fertility preservation, maternal and fetal prognosis after pregnancy in breast cancer survivors with BRCA1/2.</p><p><strong>Conclusion: </strong>According to the existing literature evidence pregnancy after therapy for breast cancer in BRCA carriers is safe for the mother and offspring, but patients' needs, oncofertility counseling and fertility-sparing strategy should be carefully planned before starting the cytotoxic treatment.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39846913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juvenile polyposis syndrome (JPS), has diverse phenotypes.
Aim: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities.
Methods: Patients' data were extracted retrospectively from 5 centers.
Results: Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 414 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017).
Conclusions: We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.
青少年息肉病综合征(JPS)具有多种表型。目的:探讨以色列不同民族JPS系的突变率、临床特征及基因型-表型相关性。方法:回顾性分析5个中心的患者资料。结果:纳入35种(49例)。31名(89%)犹太人[10名(32%)德系犹太人;9 (29%) Sephardi;11个(35%)非俄罗斯前苏联国家(NRFSU), 1个(3%)未知]。来自27个家庭的40/49个体进行了基因检测。其中,来自21个家族的34例(85,78%)发生致病性突变:BMPR1A n = 15 (71%), SMAD4 n = 6(29%)。虽然在来自NRFSU的犹太家庭中没有发现SMAD4突变,但有7个NRFSU家庭携带一个创始突变,包括BMPR1A的大基因组缺失。42例(86%)患者报告了胃肠道受累:结肠息肉(n = 40, 95%, > 50个息肉n = 14, 35%), 12例行结肠切除术。14名患者(34%)有胃或小肠受累(n = 5), 414名患者因息肉负担接受了胃切除术。来自NRFSU的家庭有更多的胃累及(66.7% vs. 22.2%-西班牙系犹太人和20%-德系犹太人;P = 0.038),胃息肉发生率较高(P = 0.017)。结论:我们证明了在以色列异种人群中有很高的突变检出率。BMPR1A突变的NRFSU患者胃受累率高。
{"title":"Phenotypic diversity among juvenile polyposis syndrome patients from different ethnic background.","authors":"Lior Haim Katz, Rachel Gingold-Belfer, Elez Vainer, Shani Hegger, Ido Laish, Estela Derazne, Ilana Weintraub, Gili Reznick-Levi, Yael Goldberg, Zohar Levi, Shlomi Cohen, Elizabeth E Half","doi":"10.1186/s13053-021-00207-9","DOIUrl":"https://doi.org/10.1186/s13053-021-00207-9","url":null,"abstract":"<p><p>Juvenile polyposis syndrome (JPS), has diverse phenotypes.</p><p><strong>Aim: </strong>To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities.</p><p><strong>Methods: </strong>Patients' data were extracted retrospectively from 5 centers.</p><p><strong>Results: </strong>Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A. GI involvement was reported in 42 patients (86%): colonic polyps (n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement (n = 5) and 414 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps (p = 0.017).</p><p><strong>Conclusions: </strong>We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39842889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-04DOI: 10.1186/s13053-021-00208-8
Elżbieta Złowocka-Perłowska, Aleksandra Tołoczko-Grabarek, Jan Lubiński
Introduction: The role of HOXB13 in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of HOXB13 p.G84E mutation in bladder and kidney cancer patients from Poland.
Materials and methods: 1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E.
Results: p.G84E mutation of HOXB13 gene was detected in three of 1418 (0.2%) bladder cancer cases and in six of 4497 controls (odds ratio [OR], 1.6; 95% CI 0.39-6.36; p = 0.8). Among 813 kidney cancer cases HOXB13 mutations was reported in three patients (0,4%) (odds ratio [OR], (OR = 2,8; 95% CI 0.69-11.11; p = 0.3). In cases with mutations in the HOXB13 gene, the family history of cancer was negative.
Conclusion: HOXB13 mutation was not associated with bladder or kidney cancer. Mutation p.G84E in HOXB13 seem not to play a role in bladder and kidney cancer development in Polish patients.
HOXB13在膀胱和肾脏肿瘤发生中的作用尚不清楚。我们的目的是确定HOXB13 p.G84E突变在波兰膀胱癌和肾癌患者中的患病率。材料与方法:对1418例膀胱癌患者、813例肾癌患者及4497例对照患者进行HOXB13 p.G84E基因分型。结果:1418例膀胱癌患者中有3例(0.2%)检测到p.G84E HOXB13基因突变,4497例对照中有6例(优势比[OR], 1.6;95% ci 0.39-6.36;p = 0.8)。在813例肾癌病例中,有3例患者报告了HOXB13突变(0.4%)(优势比[OR], (OR = 2,8;95% ci 0.69-11.11;p = 0.3)。在HOXB13基因突变的病例中,癌症家族史为阴性。结论:HOXB13突变与膀胱癌、肾癌无关。HOXB13中的p.G84E突变似乎在波兰患者的膀胱癌和肾癌发展中不起作用。
{"title":"Germline HOXB13 mutation p.G84E do not confer an increased bladder or kidney cancer risk in polish population.","authors":"Elżbieta Złowocka-Perłowska, Aleksandra Tołoczko-Grabarek, Jan Lubiński","doi":"10.1186/s13053-021-00208-8","DOIUrl":"https://doi.org/10.1186/s13053-021-00208-8","url":null,"abstract":"<p><strong>Introduction: </strong>The role of HOXB13 in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of HOXB13 p.G84E mutation in bladder and kidney cancer patients from Poland.</p><p><strong>Materials and methods: </strong>1418 patients with bladder cancer and 813 cases with kidney cancer and 4497 controls were genotyped for HOXB13 p.G84E.</p><p><strong>Results: </strong>p.G84E mutation of HOXB13 gene was detected in three of 1418 (0.2%) bladder cancer cases and in six of 4497 controls (odds ratio [OR], 1.6; 95% CI 0.39-6.36; p = 0.8). Among 813 kidney cancer cases HOXB13 mutations was reported in three patients (0,4%) (odds ratio [OR], (OR = 2,8; 95% CI 0.69-11.11; p = 0.3). In cases with mutations in the HOXB13 gene, the family history of cancer was negative.</p><p><strong>Conclusion: </strong>HOXB13 mutation was not associated with bladder or kidney cancer. Mutation p.G84E in HOXB13 seem not to play a role in bladder and kidney cancer development in Polish patients.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2022-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39874000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-14DOI: 10.1186/s13053-021-00206-w
Abdul Khalid Siraj, Tariq Masoodi, Rong Bu, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Saud Azam, Maha Al-Rasheed, Dahish Ajarim, Asma Tulbah, Fouad Al-Dayel, Khawla Sami Al-Kuraya
Background: The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited.
Methods: We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing.
Results: Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS.
Conclusions: TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.
{"title":"Prevalence of germline TP53 mutation among early onset middle eastern breast cancer patients.","authors":"Abdul Khalid Siraj, Tariq Masoodi, Rong Bu, Sandeep Kumar Parvathareddy, Kaleem Iqbal, Saud Azam, Maha Al-Rasheed, Dahish Ajarim, Asma Tulbah, Fouad Al-Dayel, Khawla Sami Al-Kuraya","doi":"10.1186/s13053-021-00206-w","DOIUrl":"https://doi.org/10.1186/s13053-021-00206-w","url":null,"abstract":"<p><strong>Background: </strong>The data on prevalence and clinical relevance of TP53 germline mutations in early onset Middle-Eastern breast cancer (BC) is limited.</p><p><strong>Methods: </strong>We determined TP53 germline mutations in a cohort of 464 early onset BC patients from Saudi Arabia using capture sequencing based next generation sequencing.</p><p><strong>Results: </strong>Germline TP53 pathogenic mutations were found in 1.5% (7/464) of early onset Saudi BC patients. A total of six pathogenic missense mutations, one stop gain mutation and two variants of uncertain significance (VUS) were detected in our cohort. No TP53 pathogenic mutations were detected among 463 healthy controls. TP53 mutations carriers were significantly more likely to have bilateral breast cancer (p = 0.0008). At median follow-up of 41 months, TP53 mutations were an unfavorable factor for overall survival in univariate analysis. All the patients carrying TP53 mutations were negative for BRCA1 and BRCA2 mutations. Majority of patients (85.7%; 6/7) carrying TP53 mutation had no family history suggestive of Li-Fraumeni Syndrome (LFS) or personal history of multiple LFS related tumors. Only one patient had a positive family history suggestive of LFS.</p><p><strong>Conclusions: </strong>TP53 germline mutation screening detects a clinically meaningful risk of early onset BC from this ethnicity and should be considered in all early onset BC regardless of the family history of cancer, especially in young patients that are negative for BRCA mutations.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39724107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.
Case presentation: A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.
Conclusions: We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.
背景:RAD51D (RAD51 para D)是原发性卵巢癌(包括输卵管癌、腹膜癌和乳腺癌)的中间癌易感基因。尽管妇科非上皮性肿瘤如子宫肉瘤与包括BRCA损伤在内的基因组不稳定性相关,但没有明确的证据表明RAD51D变异与肉瘤发展风险之间存在关系。病例介绍:一名50多岁的日本妇女因肿瘤起源于腹膜后并在腹膜复发,在大约4年的临床过程中接受了多次手术切除和几种化疗方案。腹膜肿瘤经组织学诊断为平滑肌肉瘤,并通过肿瘤谱分析作为癌症精准医学的一部分进行遗传鉴定,显示RAD51D c.904-2A > T [NM_002878]剪接变异。在遗传咨询后进行的确认性基因检测显示,在她的肿瘤中检测到的RAD51D剪接变异是种系起源的。计算机分析支持检测到的RAD51D剪接变体可能的致病性,预测由于移框导致mRNA转录衰减和蛋白产生截短,这归因于RAD51D内含子9 3'端剪接受体位点的单核苷酸改变。考虑到她的不良临床结果,显示出高度侵袭性的平滑肌肉瘤表型并改变RAD51D,本病例为RAD51D剪接变异与恶性肿瘤的发生或进展的关系提供了新的证据。我们报告这一罕见病例的发现,可能涉及RAD51D c.904-2A > T的种系变异,作为恶性肿瘤(包括平滑肌肉瘤)的潜在易感因素。结论:我们报告了一例女性患者腹膜平滑肌肉瘤的发现,该患者携带一种新的种系剪接变异RAD51D,作为该变异的致病性及其参与肉瘤病因和/或发展风险的潜在证据。据我们所知,这是第一个描述携带种系RAD51D剪接变异的平滑肌肉瘤的病例报告,并在正常转录损伤的计算预测和假设的功能蛋白生产损失的基础上阐明了其致病性。
{"title":"Retroperitoneal leiomyosarcoma in a female patient with a germline splicing variant RAD51D c.904-2A > T: a case report.","authors":"Mashu Futagawa, Hideki Yamamoto, Mariko Kochi, Yusaku Urakawa, Reimi Sogawa, Fumino Kato, Mika Okazawa-Sakai, Daisuke Ennishi, Katsunori Shinozaki, Hirofumi Inoue, Hiroyuki Yanai, Akira Hirasawa","doi":"10.1186/s13053-021-00205-x","DOIUrl":"https://doi.org/10.1186/s13053-021-00205-x","url":null,"abstract":"<p><strong>Background: </strong>RAD51D (RAD51 paralog D) is an intermediate cancer susceptibility gene for primary ovarian cancer, including fallopian tube and peritoneal carcinomas and breast cancer. Although gynecological non-epithelial tumors such as uterine sarcomas are associated with genomic instability, including BRCA impairment, there is no clear evidence of the relationship between RAD51D variants and the risk of sarcoma development.</p><p><strong>Case presentation: </strong>A Japanese woman in her 50s underwent multiple surgical resections and several regimens of chemotherapy for tumors that originated in the retroperitoneum and recurred in the peritoneum over a clinical course of approximately 4 years. The peritoneal tumor was histologically diagnosed as a leiomyosarcoma and was genetically identified to show a splice variant of RAD51D c.904-2A > T [NM_002878] through tumor profiling performed as a part of cancer precision medicine. The confirmatory genetic test performed after genetic counseling revealed that the RAD51D splicing variant detected in her tumor was of germline origin. In silico analyses supported the possible pathogenicity of the detected splice variant of RAD51D with a predicted attenuation in mRNA transcription and truncated protein production due to frameshifting, which was attributed to a single-nucleotide alteration in the splicing acceptor site at the 3'-end of intron 9 of RAD51D. Considering her unfavorable clinical outcome, which showed a highly aggressive phenotype of leiomyosarcoma with altered RAD51D, this case provided novel evidence for the relationship of a RAD51D splicing variant with malignant tumor development or progression. We report the findings of this rare case with possible involvement of the germline variant of RAD51D c.904-2A > T as a potential predisposing factor for malignant tumors, including leiomyosarcoma.</p><p><strong>Conclusions: </strong>We present the findings of a case of leiomyosarcoma in the peritoneum of a female patient with a novel germline splicing variant of RAD51D as potential evidence for the pathogenicity of the variant and its involvement in the risk of sarcoma etiology and/or development. To the best of our knowledge, this is the first case report describing a leiomyosarcoma carrying a germline RAD51D splicing variant and elucidating its pathogenicity on the basis of computational prediction of the impairment of normal transcription and the presumed loss of functional protein production.</p>","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2021-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39924811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-11-16DOI: 10.1186/s13053-021-00204-y
Karin Wallander, Håkan Thonberg, Daniel Nilsson, Emma Tham
{"title":"Correction to: Massive parallel sequencing in individuals with multiple primary tumours reveals the benefit of re-analysis.","authors":"Karin Wallander, Håkan Thonberg, Daniel Nilsson, Emma Tham","doi":"10.1186/s13053-021-00204-y","DOIUrl":"https://doi.org/10.1186/s13053-021-00204-y","url":null,"abstract":"","PeriodicalId":55058,"journal":{"name":"Hereditary Cancer in Clinical Practice","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2021-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8594138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39629421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}