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Gene Loss Associated with Poor Pancreatic Cancer Prognosis

The graphic is an example of a comparison of a normal chromosome and a chromosome with a deletion. Deletion is a type of mutation involving the loss of genetic material. It can be small, involving a single missing DNA base pair, or large, involving a piece of a chromosome.
The graphic above illustrates the loss of genetic material, or deletion, on a chromosome. (Image courtesy of the National Human Genome Research Institute.)

A recurrent alteration in the copy number of a group of genes, including the deletion of a gene known as CPGL, is associated with shorter survival times in some pancreatic cancer patients.

Pancreatic cancer is the fourth leading cause of cancer death in the United States, and the thirteenth most common cancer worldwide. Surgical resection, or removal, of cancerous tissue is the preferred treatment. Since most cases are detected in advanced stages, however, resection is possible in less than 20 percent of patients, and for these patients, median survival is 12.6 months.

 A team of CCR researchers led by Giuseppe Giaccone, M.D., Ph.D., Chief of CCR’s Medical Oncology Branch, worked with researchers from Korea, Italy, and the Netherlands to conduct a genomic analysis of tissue samples collected from small cohorts of Korean and Italian patients that had undergone surgical resection of pancreatic tumors. The researchers found a recurrent copy number loss of a cytoband, or a group of genes, known as 18q22.3, including the deletion of the carboxypeptidase of glutamate-like (CPGL) gene. They observed a significant association between shorter survival times and loss of this genetic material in both cohorts. For example, overall survival of the Korean patients with loss of 18q22.3 was 7.6 months, while overall survival for Korean patients without this copy number loss was 21.4 months. In the Italian cohort, where researchers looked for deletion of the CPGL gene as an indicator of 18q22.3 loss, the overall survival for patients whose tumors carried the deletion of this gene was 16 months, while overall survival for those without the CPGL deletion was 30.3 months.

Based on their findings, the researchers think that loss of 18q22.3 may be a marker for poor prognosis of pancreatic cancer patients with resected tumors.  Other studies have shown that CPGL is a tumor suppressor gene, so CPGL may have a role in suppressing cancer cell growth in a subset of pancreatic cancers. Separate genomic analyses have found a high frequency of the deletion of CPGL in specimens of esophageal squamous cell carcinoma and colorectal cancer, suggesting that deletion of this gene is common in several types of gastrointestinal cancers.

Reference
Lee JH, Giovannetti E, Hwang JH, Petrini I, Wang Q, Voortman J, Wang Y, Steinberg SM, Funel N, Meltzer PS, Wang Y, and Giaccone G: Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer. Clin Cancer Res. 18(2): 524-533, 2012. PubMed Link

Reviewed by Vicky Perez