4 years ago

Integrative clinical genomics of metastatic cancer

Integrative clinical genomics of metastatic cancer
Scott A. Tomlins, Erin Cobain, Marcin Cieślik, Moshe Talpaz, David C. Smith, Javed Siddiqui, Kenneth Offit, Rashmi Chugh, Xuhong Cao, Jessica Everett, Dan R. Robinson, Jeffrey Innis, Victoria Raymond, Robert J. Lonigro, Arul M. Chinnaiyan, Elena M. Stoffel, Chandan Kumar-Sinha, Pankaj Vats, Daniel F. Hayes, Laurence H. Baker, Erica Rabban, Lakshmi P. Kunju, Yi-Mi Wu, Rajen J. Mody, Ajjai Alva, David Lucas, Mark M. Zalupski, Ann F. Schott, Francis Worden, J. Scott Roberts, Joseph Vijai, Nithya Ramnath, Scott Schuetze
Metastasis is the primary cause of cancer-related deaths. Although The Cancer Genome Atlas has sequenced primary tumour types obtained from surgical resections, much less comprehensive molecular analysis is available from clinically acquired metastatic cancers. Here we perform whole-exome and -transcriptome sequencing of 500 adult patients with metastatic solid tumours of diverse lineage and biopsy site. The most prevalent genes somatically altered in metastatic cancer included TP53, CDKN2A, PTEN, PIK3CA, and RB1. Putative pathogenic germline variants were present in 12.2% of cases of which 75% were related to defects in DNA repair. RNA sequencing complemented DNA sequencing to identify gene fusions, pathway activation, and immune profiling. Our results show that integrative sequence analysis provides a clinically relevant, multi-dimensional view of the complex molecular landscape and microenvironment of metastatic cancers.

Publisher URL: http://dx.doi.org/10.1038/nature23306

DOI: 10.1038/nature23306

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.