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Risk reduction strategies for BRCA1/2 hereditary ovarian cancer syndromes: a clinical practice guideline. BRCA1/2 遗传性卵巢癌综合征的风险降低策略:临床实践指南。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-09-26 DOI: 10.1186/s13053-021-00196-9
Michelle Jacobson, Nadia Coakley, Marcus Bernardini, Kelly-Ann Branco, Laurie Elit, Sarah Ferguson, Raymond Kim

Objective: The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2.

Methods: Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners.

Results: The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria.

Conclusions: In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.

目的本指南旨在为 BRCA1 和 BRCA2 中携带致病变异或可能致病变异的女性提供相关建议:方法:根据对研究性临床试验、比较性回顾研究和指南认可所获得的证据制定了建议草案。建议草案经过了临床和方法学专家的内部审查以及临床从业人员的外部审查:结果:通过文献检索,有 1 份指南、5 篇系统综述和 15 项研究符合资格标准:不建议对 BRCA1 和 BRCA2 存在致病或可能致病变异的女性进行卵巢癌筛查。建议采用降低风险的手术来降低卵巢癌的风险。如果没有禁忌症,绝经前接受 RRSO 的妇女应接受激素治疗直至绝经。有乳腺癌病史的女性不建议接受全身激素替代治疗。对于 50 岁以下的女性,应考虑使用 RRSO 降低乳腺癌风险。确诊乳腺癌后,如果年龄小于降低卵巢癌风险的推荐年龄范围,可考虑在两年内对 BRCA1 中携带致病或可能致病变异的女性进行 RRSO 治疗,以降低乳腺癌死亡率。只有在乳腺癌肿瘤专家建议的情况下,才能考虑在 40 岁之前进行 RRSO,特别是为了治疗 BRCA2 中的乳腺癌。RRSO 后,不建议进行腹膜癌监测。
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引用次数: 0
Improving our model of cascade testing for hereditary cancer risk by leveraging patient peer support: a concept report. 利用患者同伴支持改进我们的遗传性癌症风险级联检测模式:概念报告。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-09-26 DOI: 10.1186/s13053-021-00198-7
Suzanne C O'Neill, Jada G Hamilton, Claire C Conley, Beth N Peshkin, Rosalba Sacca, Glynnis A McDonnell, Claudine Isaacs, Mark E Robson, Kenneth P Tercyak

Consensus and evidence suggest that cascade testing is critical to achieve the promise of cancer genetic testing. However, barriers to cascade testing include effective family communication of genetic risk information and family members' ability to cope with genetic risk. These barriers are further complicated by the developmental needs of unaffected family members during critical windows for family communication and adaptation. Peer support could address these barriers. We provide two illustrative examples of ongoing BRCA1/2-related clinical trials that apply a peer support model to improve family communication and functioning. Peer support can augment currently available genetic services to facilitate adjustment to and effective use of cancer genetic risk information. Importantly, this scalable approach can address the presence of cancer risk within families across multiple developmental stages. This applies a family-centered perspective that accommodates all potentially at-risk relatives. This peer support model can be further applied to emerging topics in clinical genetics to expand reach and impact.

共识和证据表明,级联检测对于实现癌症基因检测的承诺至关重要。然而,级联检测的障碍包括遗传风险信息的有效家庭沟通以及家庭成员应对遗传风险的能力。在家庭沟通和适应的关键窗口期,未受影响家庭成员的发展需求使这些障碍变得更加复杂。同伴支持可以解决这些障碍。我们提供了两个正在进行的 BRCA1/2 相关临床试验的示例,这些试验采用同伴支持模式来改善家庭沟通和功能。同伴支持可以增强目前可用的遗传服务,以促进对癌症遗传风险信息的适应和有效利用。重要的是,这种可扩展的方法可以解决家庭在多个发展阶段中存在的癌症风险问题。这就采用了以家庭为中心的视角,照顾到了所有潜在的高危亲属。这种同伴支持模式可进一步应用于临床遗传学的新兴课题,以扩大覆盖面和影响力。
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引用次数: 0
Descriptive study on subjective experience of genetic testing with respect to relationship, family planning and psychosocial wellbeing among women with lynch syndrome. 对lynch综合征妇女在关系、计划生育和心理社会健康方面基因检测主观经验的描述性研究。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-09-14 DOI: 10.1186/s13053-021-00194-x
Mari Kalamo, Johanna Mäenpää, Toni Seppälä, Jukka-Pekka Mecklin, Kirsi Pylvänäinen, Synnöve Staff

Background: Due to increased risk of endometrial and ovarian cancer, women belonging to known Lynch Syndrome (LS) families are recommended to undergo germline testing. Current practice in Finland is to offer counselling to women with pathogenic variant and advocate risk-reducing surgery (RRS) after completion of childbirth. The present study aimed to clarify the impacts of positive germline testing on family planning and reproductive decisions of these women, which are relatively unknown.

Methods: Seventy-nine carriers of germline MMR gene pathogenic variant (path_MMR) were identified from the Finnish LS Registry as having genetic testing performed before the age of 45 years and not having undergone hysterectomy or oophorectomy. These women were sent a questionnaire concerning family planning, intimate relationships and psychosocial wellbeing.

Results: Thirty-five women (44.3%) responded. Parity of path_MMR carriers (2.1) was slightly higher than parity among Finnish women in general (1.8). No significant differences were found between parity, number of induced abortions or sterilizations before and after genetic testing. Only minority of subjects reported any influence on family planning (20%) or negative impact on feminine self and body image (14%).

Conclusions: The positive germline testing does not seem to have a major negative impact on family planning, intimate relationships or feminine self and body image. According to the open comments, counselling, supportive and empathic attitude of the professionals seem to have a significant impact on this. These results are a valuable addition to the counselling of LS women at reproductive age.

背景:由于子宫内膜癌和卵巢癌的风险增加,属于已知Lynch综合征(LS)家族的女性被推荐进行种系检测。芬兰目前的做法是向携带致病变异的妇女提供咨询,并提倡在分娩后进行降低风险的手术(RRS)。本研究旨在澄清阳性生殖系检测对这些妇女的计划生育和生育决定的影响,这是相对未知的。方法:从芬兰LS登记处确定了79例生殖系MMR基因致病变异(path_MMR)携带者,这些携带者在45岁之前进行了基因检测,没有接受过子宫切除术或卵巢切除术。向这些妇女发送了一份关于计划生育、亲密关系和社会心理健康的问卷。结果:35名女性回应,占44.3%。path_MMR携带者的胎次(2.1)略高于芬兰妇女的一般胎次(1.8)。基因检测前后胎次、人工流产或绝育次数无显著差异。只有少数受试者报告对计划生育有影响(20%)或对女性自我和身体形象有负面影响(14%)。结论:生殖系检测阳性似乎不会对计划生育、亲密关系或女性自我和身体形象产生重大负面影响。根据公开评论,专业人士的咨询、支持和同情态度似乎对这一点有重大影响。这些结果对生育年龄的LS妇女的咨询是一个有价值的补充。
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引用次数: 2
Correction to: Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants. 更正:澳大利亚胰腺癌筛查项目参与者中新的生殖系致病变异的显著检测。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-09-08 DOI: 10.1186/s13053-021-00195-w
Krithika Murali, Tanya M Dwarte, Mehrdad Nikfarjam, Katherine M Tucker, Rhys B Vaughan, Marios Efthymiou, Allison Collins, Allan D Spigelman, Lucinda Salmon, Amber L Johns, David B Williams, Martin B Delatycki, Thomas John, Alina Stoita
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引用次数: 0
Population or family history based BRCA gene tests of breast cancer? A systematic review of economic evaluations. 基于人群或家族史的乳腺癌BRCA基因检测?对经济评估的系统回顾。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-08-28 DOI: 10.1186/s13053-021-00191-0
Zahra Meshkani, Ali Aboutorabi, Najmeh Moradi, Mostafa Langarizadeh, Ali Ghanbari Motlagh

Background: Nearly 56% of at-risk carriers are not identified and missed as a result of the current family-history (FH) screening for genetic testing. The present study aims to review the economic evaluation studies on BRCA genetic testing strategies for screening and early detection of breast cancer.

Methods: This systematic literature review is conducted within the Cochrane Library, PubMed, Scopus, Web of Science, ProQuest, and EMBASE databases. In this paper, the relevant published economic evaluation studies are identified by following the standard Cochrane Collaboration methods and adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement reporting some recommendations for articles up to March 2020. Thereafter, the inclusion and exclusion criteria are applied to screen the articles. Disagreements are resolved through a consensus meeting. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist is used in the evaluation of quality. Finally, a narrative synthesis is performed. To compare the different levels of incremental cost-effectiveness ratio (ICER), the net present value is calculated based on a discount rate of 3% in 2019.

Results: Among 788 initially retrieved citations, 12 studies were included. More than 60% of the studies were originated from high-income countries and were published after 2016. It is noteworthy that most of the studies evaluated the payer perspective. Moreover, the robustness of the results were analyzed through one-way and probabilistic sensitivity analyses in nearly 66% of these studies. Nearly, 25% of the studies are focused and defined population-based and family history BRCA tests as comparators; afterwards, the cost-effectiveness of the former was confirmed. The highest and lowest absolute values for the ICERs were $65,661 and $9 per quality adjusted life years, respectively. All studies met over 70% of the CHEERs criteria checklist, which was considered as 93% of high quality on average as well.

Conclusions: The genetic BRCA tests for the general population as well as unselected breast cancer patients were cost-effective in high and upper-middle income countries and those with prevalence of gene mutation while population-based genetic tests for low-middle income countries are depended on the price of the tests.

背景:由于目前的家族史(FH)基因检测筛查,近56%的高危携带者没有被识别和遗漏。本研究旨在回顾BRCA基因检测策略在癌症筛查和早期检测中的经济评价研究。方法:本系统文献综述在Cochrane图书馆、PubMed、Scopus、Web of Science、ProQuest和EMBASE数据库中进行。在本文中,相关已发表的经济评估研究是通过遵循标准的Cochrane协作方法和遵守系统评价和荟萃分析首选报告项目(PRISMA)声明来确定的,该声明报告了截至2020年3月的一些文章建议。此后,应用纳入和排除标准来筛选文章。分歧通过协商一致会议解决。综合健康经济评估报告标准(CHEERS)检查表用于质量评估。最后,进行叙事合成。为了比较不同水平的增量成本效益比(ICER),净现值是根据2019年3%的贴现率计算的。结果:在788篇最初检索到的引文中,包括12项研究。超过60%的研究来自高收入国家,发表于2016年之后。值得注意的是,大多数研究都评估了付款人的观点。此外,在近66%的研究中,通过单向和概率敏感性分析对结果的稳健性进行了分析。近25%的研究集中并定义了基于人群和家族史的BRCA检测作为对照;之后,证实了前者的成本效益。ICER的最高和最低绝对值分别为每质量调整寿命年65661美元和9美元。所有研究都符合CHEER标准检查表的70%以上,平均而言,这也被认为是93%的高质量研究。结论:在高收入和高收入国家以及基因突变流行的国家,对普通人群和未经选择的癌症患者进行BRCA基因检测具有成本效益,而中低收入国家基于人群的基因检测取决于检测价格。
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引用次数: 9
Cytotoxic and targeted therapy for BRCA1/2-driven cancers. brca1 /2驱动癌症的细胞毒性和靶向治疗。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-08-28 DOI: 10.1186/s13053-021-00193-y
Evgeny N Imyanitov

Tumors arising in BRCA1/2 germline mutation carriers usually demonstrate somatic loss of the remaining BRCA1/2 allele and increased sensitivity to platinum compounds, anthracyclines, mitomycin C and poly (ADP-ribose) polymerase inhibitors (PARPi). Exposure to conventional platinum-based therapy or PARPi results in the restoration of BRCA1/2 function and development of resistance to systemic therapy, therefore, there is a need for other treatment options. Some studies suggested that the use of specific drug combinations or administration of high-dose chemotherapy may result in pronounced tumor responses. BRCA1/2-driven tumors are characterized by increased immunogenicity; promising efficacy of immune therapy has been demonstrated in a number of preclinical and clinical investigations. There are outstanding issues, which require further consideration. Platinum compounds and PARPi have very similar mode of antitumor action and are likely to render cross-resistance to each other, so their optimal position in cancer treatment schemes may be a subject of additional studies. Sporadic tumors with somatically acquired inactivation of BRCA1/2 or related genes resemble hereditary neoplasms with regard to the spectrum of drug sensitivity; the development of user-friendly BRCAness tests presents a challenge. Many therapeutic decisions are now based on the BRCA1/2 status, so the significant reduction of the turn-around time for predictive laboratory assays is of particular importance.

BRCA1/2种系突变携带者产生的肿瘤通常表现为剩余BRCA1/2等位基因的体细胞缺失,对铂类化合物、蒽环类药物、丝裂霉素C和聚(adp -核糖)聚合酶抑制剂(PARPi)的敏感性增加。暴露于常规铂基治疗或PARPi可导致BRCA1/2功能恢复并对全身治疗产生耐药性,因此需要其他治疗方案。一些研究表明,使用特定的药物组合或给予大剂量化疗可能导致明显的肿瘤反应。brca1 /2驱动的肿瘤以免疫原性增强为特征;许多临床前和临床研究已经证明了免疫治疗的良好疗效。还有一些悬而未决的问题需要进一步考虑。铂类化合物和PARPi具有非常相似的抗肿瘤作用模式,并且可能相互产生交叉抗性,因此它们在癌症治疗方案中的最佳位置可能是一个进一步研究的主题。BRCA1/2或相关基因体获得性失活的散发性肿瘤在药物敏感性谱方面与遗传性肿瘤相似;开发用户友好的BRCAness测试提出了一个挑战。现在许多治疗决定都是基于BRCA1/2的状态,因此显著减少预测实验室分析的周转时间是特别重要的。
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引用次数: 7
Myxofibrosarcoma harboring an MLH1 pathogenic germline variant associated with Muir-Torre syndrome: a case report. 黏液纤维肉瘤携带与Muir-Torre综合征相关的MLH1致病种系变异:1例报告。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-08-21 DOI: 10.1186/s13053-021-00192-z
Makoto Nakagawa, Eisuke Kobayashi, Masayoshi Yamada, Tomoko Watanabe, Makoto Hirata, Noriko Tanabe, Mineko Ushiama, Hiromi Sakamoto, Chiaki Sato, Taisuke Mori, Akihiko Yoshida, Teruhiko Yoshida, Kokichi Sugano, Akira Kawai

Background: Muir-Torre syndrome (MTS), which accounts for a small subset (1-3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare.

Case presentation: Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV.

Conclusions: This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.

背景:Muir-Torre综合征(MTS)占Lynch综合征(LS)的一小部分(1- 3%),是一种常染色体显性遗传疾病,以皮脂腺或角状棘皮瘤与内脏恶性肿瘤相关为特征。大多数MTS家族在MSH2中有致病性种系变异(PGV)。肉瘤在LS肿瘤谱系中并不常见,与MTS相关的肉瘤极为罕见。病例介绍:我们报告一例73岁男性腹壁黏液纤维肉瘤同时发生皮脂瘤,诊断为MTS,免疫组织化学检测到MLH1和PMS2蛋白表达缺失,并证实高频微卫星不稳定性(MSI-H)。种系遗传分析显示,他携带MLH1 PGV。结论:这是首例MLH1 PGV携带者的MSI-H黏液纤维肉瘤合并MTS。虽然罕见,但我们应该认识到肉瘤可能是LS和MTS的一部分。
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引用次数: 1
Significant detection of new germline pathogenic variants in Australian Pancreatic Cancer Screening Program participants. 澳大利亚胰腺癌筛查项目参与者中新的生殖系致病变异的显著检测。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-08-16 DOI: 10.1186/s13053-021-00190-1
Krithika Murali, Tanya M Dwarte, Mehrdad Nikfarjam, Katherine M Tucker, Rhys B Vaughan, Marios Efthymiou, Allison Collins, Allan D Spigelman, Lucinda Salmon, Amber L Johns, David B Williams, Martin B Delatycki, Thomas John, Alina Stoita

Background: The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Cancer Service before or after study enrolment.

Methods: Individuals aged 40-80 years (or 10 years younger than the earliest PDAC diagnosis) were eligible for APCSP study entry if they had 1) ≥ two blood relatives with PDAC (at least one of first-degree association); 2) a clinical or genetic diagnosis of Hereditary Pancreatitis or Peutz-Jeghers syndrome irrespective of PDAC family history; or 3) a known PDAC predisposition germline pathogenic variant (BRCA2, PALB2, CDKN2A, or Lynch syndrome) with ≥one PDAC-affected first- or second-degree relative. Retrospective medical record review was conducted for APCSP participants enrolled at the participating Australian hospitals from January 2011 to December 2019. We audited the genetic investigations offered by multiple Familial Cancer Services who assessed APCSP participants according to national guidelines, local clinical protocol and/or the availability of external research-funded testing, and the subsequent findings. Descriptive statistical analysis was performed using Microsoft Excel.

Results: Of 189 kindreds (285 participants), 50 kindreds (71 participants) had a known germline pathogenic variant at enrolment (BRCA2 n = 35, PALB2 n = 6, CDKN2A n = 3, STK11 n = 3, PRSS1 n = 2, MLH1 n = 1). Forty-eight of 136 (35%) kindreds with no known germline pathogenic variant were offered mutation analysis; 89% was clinic-funded, with increasing self-funded testing since 2016. The relatively low rates of genetic testing performed reflects initial strict criteria for clinic-funded genetic testing. New germline pathogenic variants were detected in five kindreds (10.4%) after study enrolment (BRCA2 n = 3 kindreds, PALB2 n = 1, CDKN2A n = 1). Of note, only eight kindreds were reassessed by a Familial Cancer Service since enrolment, with a further 21 kindreds identified as being suitable for reassessment.

Conclusion: Germline pathogenic variants associated with PDAC were seen in 29.1% of our high-risk cohort (55/189 kindreds; 82/285 participants). Importantly, 10.4% of kindreds offered genetic testing were newly identified as having germline pathogenic variants, with majority being BRCA2. As genetic testing standards evolve rapidly in PDAC, 5-yearly reassessment of high-risk individuals by Familial Cancer Services is warranted.

背景:澳大利亚癌症筛查计划(APCSP)为胰腺导管腺癌(PDAC)风险增加的个体提供内窥镜超声监测,所有参与者在研究注册前或注册后都需要家族癌症服务机构的评估。方法:40-80岁的个体 年(或10 比最早的PDAC诊断年轻几岁)有资格参加APCSP研究,如果他们有1) ≥ 两名患有PDAC的血亲(至少一名为一级关联);2) 遗传性胰腺炎或Peutz-Jeghers综合征的临床或遗传诊断,与PDAC家族史无关;或3)已知的PDAC易感性种系致病性变体(BRCA2、PALB2、CDKN2A或Lynch综合征),具有≥一个受PDAC影响的一级或二级亲属。对2011年1月至2019年12月在参与的澳大利亚医院登记的APCSP参与者进行了回顾性医疗记录审查。我们审计了多个癌症家族服务机构提供的基因调查,这些服务机构根据国家指南、当地临床方案和/或外部研究资助测试的可用性以及随后的发现对APCSP参与者进行了评估。结果:在189个家系(285名参与者)中,50个家系在登记时有已知的种系致病性变异(BRCA2 n = 35,PALB2 n = 6,CDKN2A n = 3,STK11 n = 3,PRSS1 n = 2,MLH1 n = 1) 。136个没有已知种系致病变异株的家系中有48个(35%)进行了突变分析;89%由诊所资助,自2016年以来,自费检测不断增加。进行基因检测的比率相对较低,这反映了临床资助的基因检测最初的严格标准。研究登记后,在5个家系(10.4%)中检测到新的种系致病性变异(BRCA2 n = 3个家族,PALB2 n = 1,CDKN2A n = 1) 。值得注意的是,自注册以来,癌症家族服务机构仅对8个品种进行了重新评估,另有21个品种被确定为适合重新评估。结论:29.1%的高危队列(55/189个家系;82/285名参与者)中发现了与PDAC相关的种系致病性变异。重要的是,10.4%的提供基因检测的家族被新发现具有种系致病性变体,其中大多数是BRCA2。随着PDAC基因检测标准的快速发展,癌症家族服务机构有必要对高危人群进行5年一次的重新评估。
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引用次数: 2
Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature. 扩展E318K (c.952G > A) MITF种系突变携带者的表型:病例系列和文献综述
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-07-21 DOI: 10.1186/s13053-021-00189-8
Leandro Jonata Carvalho Oliveira, Aline Bobato Lara Gongora, Fabiola Ambrosio Silveira Lima, Felipe Sales Nogueira Amorim Canedo, Carla Vanessa Quirino, Janina Pontes Pisani, Maria Isabel Achatz, Benedito Mauro Rossi

Background: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.

Case presentation: We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.

Conclusions: Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.

背景:小眼相关转录因子基因(MITF)属于MYC超基因家族,在黑素细胞的稳态中起重要作用。携带MITF种系致病变异的个体患癌症的风险增加,最明显的是黑色素瘤和肾细胞癌。病例介绍:我们描述了一个10人的队列,他们携带相同的MITF c.952G > a (p.Glu 318Lys),或p.E318K,种系致病变异。6名携带者发生了至少一种恶性肿瘤(4例乳腺癌;1子宫颈癌;1结肠癌;1黑素瘤;1卵巢/输卵管癌)。这些个体及其亲属之间存在显著的表型异质性。总体而言,乳腺癌是该病例系列中最常见的恶性肿瘤,在先证者及其亲属中有60例(21.67%)癌症病例中有13例。结论:我们的回顾性分析数据提出了MITF p.E318K致病变异与乳腺癌风险增加可能相关的假设。
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引用次数: 2
Evaluation and comparison of hereditary Cancer guidelines in the population. 评估和比较人群中的遗传性癌症指南。
IF 1.7 4区 医学 Q3 ONCOLOGY Pub Date : 2021-07-17 DOI: 10.1186/s13053-021-00188-9
Jordon B Ritchie, Cecelia Bellcross, Caitlin G Allen, Lewis Frey, Heath Morrison, Joshua D Schiffman, Brandon M Welch

Background: Family health history (FHx) is an effective tool for identifying patients at risk of hereditary cancer. Hereditary cancer clinical practice guidelines (CPG) contain criteria used to evaluate FHx and to make recommendations for genetic consultation. Comparing different CPGs used to evaluate a common set of FHx provides insight into how well the CPGs perform, the extent of agreement across guidelines, and how well they identify patients who should consider a cancer genetic consultation.

Methods: We compare the American College of Medical Genetics and Genomics (ACMG) and the National Comprehensive Cancer Networks (NCCN) (2019) CPG criteria for FHx collected by a chatbot and evaluated by ontologies and web services in a previous study. Collected FHx met criteria from seven groups: Gene Mutation, Breast and Ovarian, Li-Fraumeni syndrome (LFS), Colorectal and Endometrial, Relative Meets Criteria, ACMG Only Criteria, and NCCN Testing. CPG Criteria were coded and matched across 12 ACMG sub-guidelines and 6 NCCN sub-guidelines for comparison purposes.

Results: The dataset contains 4915 records, of which 2221 met either ACMG or NCCN criteria and 2694 did not. There was significant overlap-1179 probands met both ACMG and NCCN criteria. The greatest similarities were for Gene Mutation and Breast and Ovarian criteria and the greatest disparity existed among Colorectal and Endometrial criteria. Only 156 positive gene mutations were reported and of the 2694 probands who did not meet criteria, 90.6% of them reported at least one cancer in their personal or family cancer history.

Conclusion: Hereditary cancer CPGs are useful for identifying patients at risk of developing cancer based on FHx. This comparison shows that with the aid of chatbots, ontologies, and web services, CPGs can be more efficiently applied to identify patients at risk of hereditary cancer. Additionally this comparison examines similarities and differences between ACMG and NCCN and shows the importance of using both guidelines when evaluating hereditary cancer risk.

背景:家族健康史(FHx)是识别遗传性癌症风险患者的有效工具。遗传性癌症临床实践指南(CPG)包含用于评估家族健康史和提出遗传咨询建议的标准。比较用于评估一组常见遗传性心脏病的不同 CPG,可以深入了解 CPG 的性能如何、各指南之间的一致程度,以及它们在确定应考虑进行癌症遗传咨询的患者方面的效果如何:我们比较了美国医学遗传学和基因组学学会(ACMG)和美国国家综合癌症网络(NCCN)(2019 年)CPG 的 FHx 标准,这些标准由聊天机器人收集,并在之前的研究中通过本体论和网络服务进行了评估。收集的 FHx 符合七个组的标准:基因突变、乳腺和卵巢、Li-Fraumeni 综合征 (LFS)、结直肠和子宫内膜、相对符合标准、ACMG 唯一标准和 NCCN 检测。为便于比较,对 CPG 标准进行了编码,并在 12 个 ACMG 子指南和 6 个 NCCN 子指南之间进行了匹配:数据集包含 4915 条记录,其中 2221 条符合 ACMG 或 NCCN 标准,2694 条不符合。其中有 1179 个探查者同时符合 ACMG 和 NCCN 标准,存在明显重叠。基因突变与乳腺癌和卵巢癌标准的相似度最高,而结肠直肠癌和子宫内膜癌标准的差异最大。仅报告了 156 例阳性基因突变,而在不符合标准的 2694 例原发性患者中,90.6% 的人报告其个人或家族癌症史中至少有一种癌症:结论:遗传性癌症 CPGs 对于根据 FHx 确定有患癌症风险的患者非常有用。这一比较表明,借助聊天机器人、本体和网络服务,CPG 可以更有效地用于识别有遗传性癌症风险的患者。此外,该比较还研究了 ACMG 和 NCCN 之间的异同,并说明了在评估遗传性癌症风险时使用这两种指南的重要性。
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Hereditary Cancer in Clinical Practice
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