Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma

  title={Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma},
  author={Carlos Caldas and Stephan A. Hahn and Lu{\'i}s Teixeira da Costa and Mark Redston and Mieke Schutte and Albert B. Seymour and Craig L. Weinstein and Ralph H. Hruban and Charles J. Yeo and Scott E. Kern},
  journal={Nature Genetics},
The MTS1 gene on chromosome 9p21 encodes the p16 inhibitor of cyclinD/Cdk-4 complexes, and is deleted or mutated in a variety of tumour types. We found allelic deletions of 9p21–p22 in 85% of pancreatic adenocarcinomas. Analysis of MTS1 in pancreatic carcinomas (27 xenografts and 10 cell lines) showed homozygous deletions in 15 (41%) and sequence changes in 14 (38%). These included eight point mutations (four nonsense, two missense and two splice site mutations) and six deletions/ insertions… 

Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas

It is suggested that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas.

Frequency of homozygous deletion at p16/CDKN2 in primary human tumours

It is found that small homozygous deletions represent the predominant mechanism of inactivation at 9p21 in bladder tumours and are present in other tumour types, including breast and prostate cancer.

Infrequent Somatic Mutation of the MTS1 Gene in Primary Bladder Carcinomas

The results indicated that inactivation of the MTS1 gene is likely to be a contributing factor in some, but not the majority of, bladder cancers.

Intragenic Homozygous Deletions of MTS1 Gene in Gastric Cancer in Taiwan

Data indicate that alterations of the MTS1 and MTS2 genes are infrequently encountered, and additional studies of LOH with more micro‐satellite markers near 9p21 are mandatory to elucidate whether another tumor suppressor gene exists in the vicinity of M TS1 in primary gastric adenocarcinoma.

Decreased expression of the p16/MTS1 gene without mutation is frequent in human urinary bladder carcinomas.

Results indicate that while p16 gene mutations may be rare, changes in the level of the p16 transcripts could play a role in human bladder carcinoma development.

Alterations of CDKN2 (p16) in non‐small cell lung cancer

In summary, inactivation of CDKN2 is implicated in the development of about 20% of NSCLC, but the possibility of another tumor suppressor gene on chromosome segment 9p21 important in lung cancer cannot be eliminated.

Mutation of p16, p21 or cyclin dependent kinase 4 is rare in acute lymphoblastic leukaemia

Results of this study showed mutation of p16, p21 or CDK4 to be rare events in Arab ALL patients.

Mutational Analysis of CDKN2 (CDK4I/MTS1) Gene in Tissues and Cell Lines of Human Prostate Cancer

The results indicate that mutation of the CDKN2 gene is rare in prostate cancer and thus does not contribute significantly to the pathogenesis of human prostate cancer.



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.

K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions.

It is indicated that mutated K-ras and p53 genes can cooperate in the establishment of ductal pancreatic cancers, whereas other genetic events have to be present in nonductal tumors.

p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions.

A review of 1937 published p53 mutations revealed that the occurrence of small (1-2 base pairs) microdeletions varied among different types of human neoplasms and that pancreatic adenocarcinoma had one of the highest frequencies.

Mutations and altered expression of p16INK4 in human cancer.

Results are consistent with the hypothesis that p16INK4 is a tumor-suppressor protein and that genetic and epigenetic abnormalities in genes controlling the G1 checkpoint can lead to both escape from senescence and cancer formation.

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.

K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization.

These results demonstrate that primer-mediated, mutant-enriched polymerase chain reaction-restriction fragment length polymorphism analysis combined with allele-specific oligonucleotide hybridization can be used to detect and characterize mutations in codon 12 of the K-ras oncogene in formalin-fixed, paraffin-embedded tissues.

Allelotype of pancreatic adenocarcinoma.

The first allelotype of pancreatic adenocarcinoma is assembled, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected neoplasms, with a value similar to that seen previously in colorectal carcinoma.

Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes.

Investigation of the expression of the p53 and Rb-1 tumor-suppressor genes in seven human pancreatic carcinoma cell lines revealed multiple abnormalities, including gross rearrangements in two cell lines, the absence of detectable p53 transcript in twocell lines and a truncated transcript in one line.