Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study. - PubMed - NCBI
Genet Med. 2017 Jan 26. doi: 10.1038/gim.2016.191. [Epub ahead of print]
Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.
Ghazani AA1,2,3,
Oliver NM1,2,
St Pierre JP2,
Garofalo A3,
Rainville IR2,4,
Hiller E2,4,
Treacy DJ1,2,
Rojas-Rudilla V5,
Wood S2,
Bair E2,
Parello M2,
Huang F2,3,
Giannakis M2,3,
Wilson FH2,3,
Stover EH2,3,
Corsello SM2,3,
Nguyen T2,
Rana HQ2,4,
Church AJ6,
Lowenstein C2,
Cibulskis C3,
Amin-Mansour A3,
Heng J2,
Brais L2,
Santos A2,
Bauer P2,
Waldron A2,
Lo P2,
Gorman M2,
Lydon CA2,
Welch M2,
McNamara P2,
Gabriel S3,
Sholl LM5,
Lindeman NI5,
Garber JE2,4,
Joffe S7,
Van Allen EM1,2,3,
Gray SW2,
Ja Nne PA2,
Garraway LA1,2,3,
Wagle N1,2,3.
Abstract
PURPOSE:
Implementing cancer precision medicine in the clinic requires assessing the therapeutic relevance of genomic alterations. A main challenge is the systematic interpretation of whole-exome sequencing (WES) data for clinical care. METHODS:
One hundred sixty-five adults with metastatic colorectal and lung adenocarcinomas were prospectively enrolled in the CanSeq study. WES was performed on DNA extracted from formalin-fixed paraffin-embedded tumor biopsy samples and matched blood samples. Somatic and germ-line alterations were ranked according to therapeutic or clinical relevance. Results were interpreted using an integrated somatic and germ-line framework and returned in accordance with patient preferences. RESULTS:
At the time of this analysis, WES had been performed and results returned to the clinical team for 165 participants. Of 768 curated somatic alterations, only 31% were associated with clinical evidence and 69% with preclinical or inferential evidence. Of 806 curated germ-line variants, 5% were clinically relevant and 56% were classified as variants of unknown significance. The variant review and decision-making processes were effective when the process was changed from that of a Molecular Tumor Board to a protocol-based approach. CONCLUSION:
The development of novel interpretive and decision-support tools that draw from scientific and clinical evidence will be crucial for the success of cancer precision medicine in WES studies.Genet Med advance online publication 26 January 2017Genetics in Medicine (2017); doi:10.1038/gim.2016.191.
- [PubMed - as supplied by publisher]
No hay comentarios:
Publicar un comentario