TY - JOUR
T1 - Integrative molecular analysis of patients with advanced and metastatic cancer
AU - Sailer, Verena
AU - Wa, Kenneth
AU - Zhang, Tuo
AU - Bareja, Rohan
AU - Pisapia, David J.
AU - Sigaras, Alexandros
AU - Bhinder, Bhavneet
AU - Romanel, Alessandro
AU - Wilkes, David
AU - Sticca, Evan
AU - Cyrta, Joanna
AU - Rao, Rema
AU - Sahota, Sheena
AU - Pauli, Chantal
AU - Beg, Shaham
AU - Motanagh, Samaneh
AU - Kossai, Myriam
AU - Fontugne, Jacqueline
AU - Puca, Loredana
AU - Rennert, Hanna
AU - Xiang, Jenny Zhaoying
AU - Greco, Noah
AU - Kim, Rob
AU - MacDonald, Theresa Y.
AU - McNary, Terra
AU - Blattner-Johnson, Mirjam
AU - Schiffman, Marc H.
AU - Faltas, Bishoy M.
AU - Greenfield, Jeffrey P.
AU - Rickman, David
AU - Andreopoulou, Eleni
AU - Holcomb, Kevin
AU - Vahdat, Linda T.
AU - Scherr, Douglas S.
AU - van Besien, Koen
AU - Barbieri, Christopher E.
AU - Robinson, Brian D.
AU - Alan Fine, Howard
AU - Ocean, Allyson J.
AU - Molina, Ana
AU - Shah, Manish A.
AU - Nanus, David M.
AU - Pan, Qiulu
AU - Demichelis, Francesca
AU - Tagawa, Scott T.
AU - Song, Wei
AU - Mosquera, Juan Miguel
AU - Sboner, Andrea
AU - Rubin, Mark A.
AU - Elemento, Olivier
AU - Beltran, Himisha
N1 - Funding Information:
Supported by the Englander Institute for Precision Medicine of Weill Cornell Medicine and New York Presbyterian, the Translational Research Program of the Department of Pathology and Laboratory Medicine at Weill Cornell Medicine. Funded by Department of Defense Grants No. PC121341 (H.B.) and PC160264 (D.R., H.B.), the Prostate Cancer Foundation (L.P., M.A.R., and H.B.), and National Cancer Institute SPORE in Prostate Cancer Grant No. P50-CA211024 (J.M.M., M.A.R., O.E., and H.B.).
Publisher Copyright:
© 2019 by American Society of Clinical Oncology
PY - 2019
Y1 - 2019
N2 - 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 TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 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.
AB - 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 TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 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.
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U2 - 10.1200/PO.19.00047
DO - 10.1200/PO.19.00047
M3 - Article
AN - SCOPUS:85080860385
SN - 2473-4284
VL - 3
SP - 1
EP - 12
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -
