Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene is Associated with Poor Prognosis in Resected Pancreatic Cancer

Overview

Journal Clin Cancer Res

Specialty Oncology

Date 2011 Dec 1

PMID 22128300

Citations 14

Authors

Jih-Hsiang Lee

Elisa Giovannetti

Jin-Hyeok Hwang

Iacopo Petrini

Qiuyan Wang

Johannes Voortman

Yonghong Wang

Seth M Steinberg

Niccola Funel

Paul S Meltzer

Yisong Wang

Giuseppe Giaccone

Affiliations

Soon will be listed here.

Abstract

Purposes: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted.

Experimental Design: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells.

Results: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation.

Conclusion: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer.

Citing Articles

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