Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas

  title={Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas},
  author={Detlef Bartsch and Douglas W. Shevlin and William S Tung and Oliver Kisker and Samuel A. Jr. Wells and Paul J. Goodfellow},
The gene encoding the cell‐cycle regulatory protein p16, CDKN2, is localized on chromosome band 9p21. CDKN2 is frequently deleted or mutated in a variety of tumor cell lines, including pancreatic cancer cell lines and xenografts, as well as in some primary tumors. We examined 32 primary pancreatic adenocarcinomas for CDKN2 mutations and for loss of heterozygosity of 9p21 sequences to assess the role of CDKN2 in pancreatic carcinogenesis. Single‐strand conformation variant analysis (SSCV) and… 

Frequent abnormalities of the putative tumor suppressor gene FHIT at 3p14.2 in pancreatic carcinoma cell lines.

The FHIT gene may be a target tumor suppressor gene involved in pancreatic carcinogenesis and is localized on chromosome 3p14, a region including a tumor cell-specific, commonly deleted region.

Alterations of CDKN2 (MTS1/p16INK4A) gene in paraffin-embedded tumor tissues of human stomach, lung, cervix and liver cancers

Results suggest that mutations of the CDKN2 gene might be an important genetic change in NSCLCs, cervix cancers and hepatocellular carcinomas.

p16(MTS-1/CDKN2/INK4a) in cancer progression.

P16 is a major tumor-suppressor gene whose frequent loss occurs early in many human cancers and is believed that loss of p16 is an early and often critical event in tumor progression.

Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors

The results suggest that DPC4 is an important target gene promoting tumorigenesis of non-functioning neuroendocrine pancreatic carcinomas.

Molecular pathogenesis of pancreatic cancer.

This chapter will provide an overview of the molecular pathogenesis of pancreatic cancer with emphasis on clinical applications and mechanism-based therapies for patients with advanced disease.

Pancreatic carcinoma in carriers of a specific 19 base pair deletion of CDKN2A/p16 (p16-leiden).

The p16-Leiden deletion was associated with progression toward conventional ductal adenocarcinomas in all cases but one and might also indicate that chemoprevention needs consideration.

The CDKN2A (p16) Gene and Human Cancer

The known mutations in p16CDKN2A are tabulated and specific aspects, particularly with respect to germline mutations and cancer predisposition are discussed.

Molecular diagnosis of pancreas carcinoma

  • T. Chu
  • Biology, Medicine
    Journal of clinical laboratory analysis
  • 1997
These emerging molecular genetic biomarkers are associated with regulation of cell growth and recognition, as well as gene expression, and may offer new insight into the cellular precursors to and genesis of pancreas cancer.



Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas.

The results suggest that the mutation of the CDKN2 gene may not be a critical genetic change in the formation of primary breast carcinoma.

Somatic mutations of the MTS (multiple tumor suppressor) 1/CDK4l (cyclin-dependent kinase-4 inhibitor) gene in human primary non-small cell lung carcinomas.

The results suggest that inactivation of MTS1/CDK4l plays an important role during carcinogenesis of NSCLC.

Rates of p16 (MTS1) mutations in primary tumors with 9p loss.

It is concluded that p16 is not the primary target of 9p21-22 loss in a large number of nonmelanoma primary tumors.

Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin-dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma.

Results suggested that the MTS1/CDK4I gene is a tumor suppressor the inactivation of which plays an important role during carcinogenesis of the squamous cell type of esophageal carcinoma.

Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.

The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16 / CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.

Rarity of somatic and germline mutations of the cyclin-dependent kinase 4 inhibitor gene, CDK4I, in melanoma.

Evidence from cytogenetics, multipoint linkage analyses of familial melanoma, and loss of heterozygosity studies of familial and sporadic melanomas support localization of a melanoma susceptibility

The MTS1 gene is frequently mutated in primary human esophageal tumors.

Esophageal cancer is one primary human tumor in which MTS1 constitutes an apparent target of heterozygous or homozygous deletions occurring at chromosome 9p21, where nucleotide substitutions identical to two of these stop codons were previously reported in other tumor types.

A cell cycle regulator potentially involved in genesis of many tumor types.

Findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues.