Assessing the Mutation Profile in Colorectal Carcinoma Using Next Generation Sequencing

Document Type

Conference Proceeding

Publication Date

1-2018

Publication Title

American Journal of Clinical Pathology

Abstract

Objectives: Over 40,000 diagnoses of locally advanced rectal cancer are made yearly in the United States, and only 40%-60% of cases respond to presurgical chemotherapy and radiation. Even fewer patients completely respond to chemoradiation. Identifying genetic biomarkers to help predict which patients may respond to therapy could help direct treatment. Next-generation sequencing (NGS) has made it possible to screen for variants in large panels of genes. Our goal is to compare mutation profiles in patients who experienced complete response to therapy against those who had a poor response (little to no tumor kill). Methods: We collected formalin-fixed paraffin-embedded (FFPE) tissue from rectal adenocarcinoma biopsies from patients (n = 12) with complete response to therapy before surgery and biopsies with corresponding surgical resection specimens from poor responders (n = 12). NGS using the Human Comprehensive Cancer Targeted Panel (Qiagen, Germantown, MD), which screens for variants in 160 genes commonly mutated in cancer, was performed on the specimens. Results: The analysis in poor responders to treatment revealed mutations in several genes, including a number previously identified in colorectal cancer. Of note, variants in FGFR3, PIK3R1, EP300, and PTEN were found. Interestingly an additional gene, GNAQ, was mutated in each poor responder case, either in the biopsy or surgical specimen. Conclusion: GNAQ codes for a guanine nucleotide-binding protein that couples transmembrane receptors to intracellular signaling pathways. Previously, GNAQ mutations have been reported in melanoma and some ocular and spinal cord neoplasms. It is a novel mutation identified in rectal carcinoma, only rarely reported in common solid tumors and leukemias. GNAQ may prove to be a diagnostic tool in predicting a response to treatment in rectal cancer. Our goal is to confirm these mutations, including GNAQ, in additional poor responder cases and compare the overall mutation profile to patients with a complete response.

Volume

149

Issue

Suppl 1

First Page

S140

Comments

American Society for Clinical Pathology (ASCP) Annual Meeting, November 2-5, 2018, Kissimmee, FL

Last Page

S140

DOI

10.1093/ajcp/aqx127.323

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