Clinicopathologic and Molecular Features of Pancreatic Ductal Adenocarcinomas Harboring Alterations in COMPASS-like Complex Genes.

TitleClinicopathologic and Molecular Features of Pancreatic Ductal Adenocarcinomas Harboring Alterations in COMPASS-like Complex Genes.
Publication TypeJournal Article
Year of Publication2023
AuthorsHissong E, Zhao L, Shi J
JournalArch Pathol Lab Med
Volume147
Issue9
Pagination1050-1059
Date Published2023 Sep 01
ISSN1543-2165
KeywordsAdenocarcinoma, Carcinoma, Pancreatic Ductal, Carcinoma, Squamous Cell, Epigenesis, Genetic, Humans, Mutation, Pancreatic Neoplasms
Abstract

CONTEXT.—: Recent genome-wide sequencing studies have identified a subset of pancreatic ductal adenocarcinomas (PDACs) harboring significant alterations in epigenetic regulation genes, including the COMPASS-like complex genes. Whether this subset of PDACs has specific histologic characteristics or carries prognostic or therapeutic implications is unknown.

OBJECTIVE.—: To determine the specific clinicopathologic and molecular features of PDACs carrying mutations in COMPASS-like complex genes.

DESIGN.—: We analyzed a series of 103 primary and metastatic PDACs with comprehensive molecular profiling, including 13 PDACs carrying loss-of-function COMPASS-like complex gene alterations (study cohort). Another 45 patients carrying PDACs with wild-type COMPASS-like complex genes were used as the control group.

RESULTS.—: PDACs within the study cohort were smaller, harboring frequent areas of poor differentiation and concurrent alterations in KRAS, TP53, SMAD4, and CDKN2A. A subset of metastatic PDACs from the study cohort showed squamous differentiation. There was a trend toward decreased survival in the study group. We further interrogated 2 public data sets and found that PDACs with COMPASS-like complex gene alterations have increased rates of TP53 mutation, body-tail location, poor differentiation or undifferentiated histology, and a higher death rate.

CONCLUSIONS.—: COMPASS-like complex gene alterations likely represent a subset of more aggressive PDACs with poor or squamous differentiation histologically and increased concurrent TP53 mutations. These findings may have potential prognostic and therapeutic implications.

DOI10.5858/arpa.2022-0103-OA
Alternate JournalArch Pathol Lab Med
PubMed ID36508685
PubMed Central IDPMC10261500
Grant ListK08 CA234222 / CA / NCI NIH HHS / United States
R37 CA262209 / CA / NCI NIH HHS / United States
Related Faculty: 
Erika Hissong, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700