Integrative Molecular Analysis of Patients With Advanced and Metastatic Cancer.

TitleIntegrative Molecular Analysis of Patients With Advanced and Metastatic Cancer.
Publication TypeJournal Article
Year of Publication2019
AuthorsSailer V, Eng KWa, Zhang T, Bareja R, Pisapia DJ, Sigaras A, Bhinder B, Romanel A, Wilkes D, Sticca E, Cyrta J, Rao R, Sahota S, Pauli C, Beg S, Motanagh S, Kossai M, Fontunge J, Puca L, Rennert H, Xiang JZhaoying, Greco N, Kim R, MacDonald TY, McNary T, Blattner-Johnson M, Schiffman MH, Faltas BM, Greenfield JP, Rickman D, Andreopoulou E, Holcomb K, Vahdat LT, Scherr DS, van Besien K, Barbieri CE, Robinson BD, Fine HAlan, Ocean AJ, Molina A, Shah MA, Nanus DM, Pan Q, Demichelis F, Tagawa ST, Song W, Mosquera JMiguel, Sboner A, Rubin MA, Elemento O, Beltran H
JournalJCO Precis Oncol
Date Published2019

PURPOSE: We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis.

PATIENTS AND METHODS: Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated.

RESULTS: Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were (33%), (11%), (10%), (8%), (8%), and (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently (1.9%), (1.5%), (1.5%), and (1.4%). Novel gene fusions were identified, including a fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant.

CONCLUSION: Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples.

Alternate JournalJCO Precis Oncol
PubMed ID31592503
PubMed Central IDPMC6778956
Grant ListP50 CA211024 / CA / NCI NIH HHS / United States