Faculty Collaboration Database

Next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas Demonstrates Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas. Arch Pathol Lab Med 2016 Jun;140(6):529-35

Date

11/05/2015

Pubmed ID

26536055

DOI

10.5858/arpa.2015-0261-SA

Scopus ID

2-s2.0-84971422004 (requires institutional sign-in at Scopus site)   16 Citations

Abstract

CONTEXT: -Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations.

OBJECTIVE: -To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma.

DESIGN: -Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations.

RESULTS: -Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4.

CONCLUSIONS: -The somatic mutations identified in our rectal adenocarcinoma cohort showed a strong correlation to those previously characterized in colonic adenocarcinoma. In addition, most rectal adenocarcinomas harbored identical somatic mutations in both the primary tumor and metastasis. These findings demonstrate evidence that rectal adenocarcinoma follows a similar molecular pathogenesis as colonic adenocarcinoma and that sampling either the primary or metastatic lesion is valid for initial evaluation of somatic mutations and selection of possible targeted therapy.

Author List

Crumley SM, Pepper KL, Phan AT, Olsen RJ, Schwartz MR, Portier BP

Author

Alexandria T. Phan MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Adenomatous Polyposis Coli Protein
Cell Cycle Proteins
Chromogranins
Class I Phosphatidylinositol 3-Kinases
Colonic Neoplasms
F-Box Proteins
F-Box-WD Repeat-Containing Protein 7
Female
GTP Phosphohydrolases
GTP-Binding Protein alpha Subunits, Gs
High-Throughput Nucleotide Sequencing
Humans
Male
Membrane Proteins
Middle Aged
Mutation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins B-raf
Proto-Oncogene Proteins p21(ras)
Receptor, Fibroblast Growth Factor, Type 3
Rectal Neoplasms
Smad4 Protein
Tumor Suppressor Protein p53
Ubiquitin-Protein Ligases