Pub Date : 2018-08-01DOI: 10.1158/1557-3125.ADVBC17-IA19
O. Olopade
Analysis of cancer genomes has rapidly become an integral part of the practice of clinical oncology, with implications for diagnosis, prognosis, treatment, and prevention. Inherited and sporadic cancers often share common mutational events. When inherited mutations are identified, genetic counseling is an essential component of care. Pathogenic BRCA1 and BRCA2 mutations are the strongest predictors of breast cancer risk and may be the strongest predictors of other inherited forms of solid tumors and hematologic malignancies as well. Waiting to treat advanced breast cancer with targeted therapies is a failure of primary prevention, and population-based strategies for risk management in high-risk populations will be needed. Understanding breast cancer progression in genetic defined subgroups has the potential to accelerate progress in precision medicine. I will discuss ongoing research in our group, our recent findings in defining the genomic landscape of early-onset breast cancer, and future directions for the early detection, treatment, and prevention of breast cancer in high-risk populations. Citation Format: Olufunmilayo I. Olopade. Homologous recombination repair deficiency and breast cancer progression in high-risk populations [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA19.
癌症基因组分析已迅速成为临床肿瘤学实践的一个组成部分，对诊断、预后、治疗和预防具有重要意义。遗传性和散发性癌症通常具有共同的突变事件。当确定遗传突变时，遗传咨询是护理的重要组成部分。致病性BRCA1和BRCA2突变是乳腺癌风险的最强预测因子，也可能是其他遗传性实体瘤和血液恶性肿瘤的最强预测因子。等待用靶向治疗治疗晚期乳腺癌是一级预防的失败，需要在高危人群中实施基于人群的风险管理策略。了解乳腺癌在遗传定义亚群中的进展有可能加速精准医学的进展。我将讨论我们小组正在进行的研究，我们在定义早发性乳腺癌的基因组图谱方面的最新发现，以及在高危人群中早期检测、治疗和预防乳腺癌的未来方向。引文格式:Olufunmilayo I. Olopade。高危人群同源重组修复缺陷与乳腺癌进展[摘要]。摘自:AACR特别会议论文集:乳腺癌研究进展;2017年10月7-10日;费城(PA): AACR;中华肿瘤杂志，2018;16(8):1 - 9。
{"title":"Abstract IA19: Homologous recombination repair deficiency and breast cancer progression in high-risk populations","authors":"O. Olopade","doi":"10.1158/1557-3125.ADVBC17-IA19","DOIUrl":"https://doi.org/10.1158/1557-3125.ADVBC17-IA19","url":null,"abstract":"Analysis of cancer genomes has rapidly become an integral part of the practice of clinical oncology, with implications for diagnosis, prognosis, treatment, and prevention. Inherited and sporadic cancers often share common mutational events. When inherited mutations are identified, genetic counseling is an essential component of care. Pathogenic BRCA1 and BRCA2 mutations are the strongest predictors of breast cancer risk and may be the strongest predictors of other inherited forms of solid tumors and hematologic malignancies as well. Waiting to treat advanced breast cancer with targeted therapies is a failure of primary prevention, and population-based strategies for risk management in high-risk populations will be needed. Understanding breast cancer progression in genetic defined subgroups has the potential to accelerate progress in precision medicine. I will discuss ongoing research in our group, our recent findings in defining the genomic landscape of early-onset breast cancer, and future directions for the early detection, treatment, and prevention of breast cancer in high-risk populations. Citation Format: Olufunmilayo I. Olopade. Homologous recombination repair deficiency and breast cancer progression in high-risk populations [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA19.","PeriodicalId":20534,"journal":{"name":"Proceedings of The 1st International Electronic Conference on Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89828999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-08-01DOI: 10.1158/1557-3125.ADVBC17-IA20
M. Murphy
In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.
除了在散发性癌症中经常发生突变外，p53肿瘤抑制因子还包含几个编码区变异，这些变异会改变功能并增加癌症风险。我们之前发表过p53的Pro47Ser变体存在于大约1-2%的非洲裔个体中，并且这种变异阻止了p53的关键磷酸化事件，并降低了该蛋白诱导细胞死亡的能力(1)。我们最近发表了该变体的小鼠模型，并表明该小鼠具有惊人的散发性癌症发病率，主要是肝细胞癌，但也包括胰腺癌，胃癌和肠癌。在一组患有乳腺癌的非裔美国妇女中，我们发现了Pro47Ser与绝经前癌症发病率相关的证据(HR 1.7, p 1)。李霞，杜蒙P, Della Pietra A, Shetler C, Murphy ME。p53密码子47多态性在功能上是显著的。生物化学学报，2005;28(2):444 - 444。PubMed PMID: 15851479。2. 莫菲梅，刘思，姚思，等。非裔美国女性TP53与乳腺癌风险的功能显著SNP。中华医学杂志2017;3:5。PubMed Central PMCID: PMC5445618。3.Jennis M, Kung CP, Basu S，等。在小鼠模型中，非洲特异性的TP53基因多态性损害了p53肿瘤抑制功能。基因工程学报，2016;30(8):918-30。PubMed Central PMCID: PMC4840298。4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME。p53的非洲特异性S47多态性改变了化疗敏感性。Cell Cycle 2016;15(19):2557-60。PubMed Central PMCID: PMC5053554。引用格式:Maureen E. Murphy。肿瘤抑制基因TP53的编码区变异可能是非洲裔美国人癌症差异的基础[摘要]。摘自:AACR特别会议论文集:乳腺癌研究进展;2017年10月7-10日;费城(PA): AACR;癌症学报，2018;16(8):1 - 2。
{"title":"Abstract IA20: A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans","authors":"M. Murphy","doi":"10.1158/1557-3125.ADVBC17-IA20","DOIUrl":"https://doi.org/10.1158/1557-3125.ADVBC17-IA20","url":null,"abstract":"In addition to being frequently mutated in sporadic cancer, the p53 tumor suppressor also contains several coding region variants that alter function and can contribute to increased cancer risk. We previously published that the Pro47Ser variant of p53 exists in approximately 1-2% of individuals of African descent, and that this variation prevents a key phosphorylation event on p53, and reduces the ability of this protein to induce cell death (1). We recently published a mouse model for this variant, and show that this mouse develops a striking incidence of sporadic cancer, predominantly hepatocellular cancer but also including cancers of the pancreas, stomach, and intestine. In a cohort of African American women with breast cancer, we found evidence for an association of Pro47Ser with pre-menopausal cancer incidence (HR 1.7, p 1. Li X, Dumont P, Della Pietra A, Shetler C, Murphy ME. The codon 47 polymorphism in p53 is functionally significant. J Biol Chem 2005;280(25):24245-51. PubMed PMID: 15851479. 2. Murphy ME, Liu S, Yao S, et al. A functionally significant SNP in TP53 and breast cancer risk in African-American women. NPJ Breast Cancer 2017;3:5. PubMed Central PMCID: PMC5445618. 3. Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016;30(8):918-30. PubMed Central PMCID: PMC4840298. 4. Basu S, Barnoud T, Kung CP, Reiss M, Murphy ME. The African-specific S47 polymorphism of p53 alters chemosensitivity. Cell Cycle 2016;15(19):2557-60. PubMed Central PMCID: PMC5053554. Citation Format: Maureen E. Murphy. A coding region variant in the TP53 tumor-suppressor gene may underlie cancer disparities in African Americans [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr IA20.","PeriodicalId":20534,"journal":{"name":"Proceedings of The 1st International Electronic Conference on Cancers: Exploiting Cancer Vulnerability by Targeting the DNA Damage Response","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73823346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：