Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma

Matthew K Stein; Forrest W Williard; Joanne Xiu; Miriam W Tsao; Michael G Martin; Benjamin W Deschner; Paxton V Dickson; Evan S Glazer; Danny Yakoub; David Shibata; Axel F Grothey; Philip A Philip; Jimmy J Hwang; Anthony F Shields; John L Marshall; W Michael Korn; Heinz-Josef Lenz; Jeremiah L Deneve

doi:10.1002/jso.25899

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Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma

Journal article

Peer reviewed

Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma

Matthew K Stein, Forrest W Williard, Joanne Xiu, Miriam W Tsao, Michael G Martin, Benjamin W Deschner, Paxton V Dickson, Evan S Glazer, Danny Yakoub, David Shibata, …

Journal of surgical oncology, Vol.121(8), pp.1320-1328

2020-06

DOI: https://doi.org/10.1002/jso.25899

PMID: 32166754

Abstract

GNAS

colon

BRAF

KRAS

molecular profile

carcinomatosis

Peritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined. We compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next-generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test-defined as pathogenic (PATH). Six hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right-sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left-sided PM. Nine percent of pCRC and 6% of PM were MSI-high (P = NS). There was no difference in TMB-high, TMB-intermediate, or TMB-low between PM and pCRC. PM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.111 Liver & Colon Cancer; 1.111.557 Metastatic Colorectal Cancer
Web Of Science research areas: Oncology; Surgery
ESI research areas: Clinical Medicine

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Details

Title: Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma
Creators: Matthew K Stein - Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
Forrest W Williard - College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
Joanne Xiu - Caris Life Sciences, Phoenix, Arizona
Miriam W Tsao - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Michael G Martin - Deparment of Hematology/Oncology, West Cancer Center, Memphis, Tennessee
Benjamin W Deschner - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Paxton V Dickson - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Evan S Glazer - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Danny Yakoub - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
David Shibata - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Axel F Grothey - Deparment of Hematology/Oncology, West Cancer Center, Memphis, Tennessee
Philip A Philip - Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
Jimmy J Hwang - Division of Hematology/Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina
Anthony F Shields - Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
John L Marshall - Division of Hematology/Oncology, Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia
W Michael Korn - Caris Life Sciences, Phoenix, Arizona
Heinz-Josef Lenz - Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California
Jeremiah L Deneve - Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee
Publication Details: Journal of surgical oncology, Vol.121(8), pp.1320-1328
Language: English
Resource Type: Journal article
PMID: 32166754
Record Identifier: 991031615309502976