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Identification of Driver Mutations in Rare Cancers: The Role of SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT)

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Disease Gene Identification

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1706))

Abstract

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.

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Acknowledgments

The authors thank the SCCOHT patients, families, clinicians, and support and advocacy groups for their critically important contributions to the IRB-approved study performed at TGen. Our work results from a multi-institutional effort and we thank the many scientists and clinicians who have contributed to this work, as well as Drs. Jeffrey Trent, David Huntsman, and Bernard Weissman for their leadership in these collaborations. Our work has been supported by grants from the National Institutes of Health (R01 CA195670-01), the Anne Rita Monahan Foundation, the Marsha Rivkin Center for Ovarian Cancer Research, the Ovarian Cancer Alliance of Arizona, the Small Cell Ovarian Cancer Foundation, and philanthropic support to the TGen Foundation.

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Authors and Affiliations

  1. Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ, 85004, USA

    Jessica D. Lang & William P. D. Hendricks

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  1. Jessica D. Lang
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  2. William P. D. Hendricks
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Correspondence to William P. D. Hendricks .

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  1. Translational Genomics Research Institute, Phoenix, Arizona, USA

    Johanna K. DiStefano

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Lang, J.D., Hendricks, W.P.D. (2018). Identification of Driver Mutations in Rare Cancers: The Role of SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT). In: DiStefano, J. (eds) Disease Gene Identification. Methods in Molecular Biology, vol 1706. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7471-9_20

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  • DOI: https://doi.org/10.1007/978-1-4939-7471-9_20

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7470-2

  • Online ISBN: 978-1-4939-7471-9

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