Identifying germline-somatic and synthetic lethal targets in hereditary cancers

广泛的分子数据越来越多地用于临床肿瘤学，以确定对治疗方案的反应的预测因子或获得预后信息。虽然生殖系基因检测已经进入了这种情况下使用的数据（通过BRCA 1/2和PARP抑制），但其他潜在的关系和目标迄今尚未得到很好的表征。在我最近来到国家癌症研究所之后，我们打算描述患有Li Fraumeni综合征或遗传性乳腺癌和卵巢癌综合征（生殖系BRCA 1/2致病性变异）的原发性乳腺癌患者的体细胞基因组和转录组模式。我们将使用这些信息，从生物信息学的角度来确定特定的靶向治疗或具有潜在的生殖系突变的合成致死靶点的治疗是否可能是相对于标准治疗的肿瘤治疗的过度代表性候选者。

Extensive molecular data is increasingly used in clinical oncology to identify predictors of response to therapeutic options or to gain prognostic information. While germline genetic testing has entered the data used in this context (via BRCA1/2 and PARP inhibition), other potential relationships and targets have not been well characterized to date. Following my recent arrival to the National Cancer Institute, we intend to characterize somatic genomic and transcriptomic patterns from primary breast cancers in patients who have either Li Fraumeni syndrome or hereditary breast and ovarian cancer syndrome (germline BRCA1/2 pathogenic variants). We will use this information to determine from a bioinformatics standpoint if specific targeted therapies or therapies with potential synthetic lethal targets to the germline mutations may be overrepresented candidates for tumor treatment relative to the standard of care.