Lang Jessica D, Hendricks William P D
Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ, 85004, USA.
Methods Mol Biol. 2018;1706:367-379. doi: 10.1007/978-1-4939-7471-9_20.
Cancer is a complex genetic disease that can arise through the stepwise accumulation of mutations in oncogenes and tumor suppressor genes in a variety of different tissues. While the varied landscapes of mutations driving common cancer types such as lung, breast, and colorectal cancer have been comprehensively charted, the genetic underpinnings of many rare cancers remain poorly defined. Study of rare cancers faces unique methodological challenges, but collaborative enterprises that incorporate next generation sequencing, reach across disciplines (i.e., pathology, genetic epidemiology, genomics, functional biology, and preclinical modeling), engage advocacy groups, tumor registries, and clinical specialists are adding increasing resolution to the genomic landscapes of rare cancers. Here we describe the approaches and methods used to identify SMARCA4 mutations, which drive development of the rare ovarian cancer, small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and point to the broader relevance of this paradigm for future research in rare cancers.
癌症是一种复杂的基因疾病，可通过多种不同组织中癌基因和肿瘤抑制基因的突变逐步积累而产生。虽然驱动常见癌症类型（如肺癌、乳腺癌和结直肠癌）的各种突变情况已得到全面描绘，但许多罕见癌症的遗传基础仍不清楚。对罕见癌症的研究面临独特的方法学挑战，但整合了下一代测序技术、跨学科（即病理学、遗传流行病学、基因组学、功能生物学和临床前建模）开展工作、与倡导团体、肿瘤登记处及临床专家合作的项目，正不断提高对罕见癌症基因组情况的解析度。在此，我们描述了用于识别SMARCA4突变的方法，这些突变驱动了罕见的卵巢癌——高钙血症型卵巢小细胞癌（SCCOHT）的发展，并指出了这一模式对未来罕见癌症研究的更广泛意义。
