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

@article{Caldas1994FrequentSM,
  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},
  year={1994},
  volume={8},
  pages={27-32}
}
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… Expand
Frequent mutations of CDKN2 in primary pancreatic adenocarcinomas
TLDR
It is suggested that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas. Expand
Frequency of homozygous deletion at p16/CDKN2 in primary human tumours
TLDR
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. Expand
Infrequent Somatic Mutation of the MTS1 Gene in Primary Bladder Carcinomas
TLDR
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. Expand
Intragenic Homozygous Deletions of MTS1 Gene in Gastric Cancer in Taiwan
TLDR
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. Expand
Homozygous deletions of the CDKN2 gene and loss of heterozygosity of 9p in primary hepatocellular carcinoma.
TLDR
The results suggest that inactivation of the CDKN2 gene in HCC is a frequent event in which homozygous deletions are the most common mechanism of CD KN2 inactivation. Expand
Decreased expression of the p16/MTS1 gene without mutation is frequent in human urinary bladder carcinomas.
TLDR
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. Expand
Alterations of CDKN2 (p16) in non‐small cell lung cancer
TLDR
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. Expand
Loss of heterozygosity at 9p21 loci and mutations of the MTS1 and MTS2 genes in human lung cancers
TLDR
DNA analysis from 30 primary lung cancers suggested that mutations of the MTS1 gene are associated with at least some human lung cancers. Expand
Selective deletion of p14(ARF) exon 1beta of the INK4a locus in oral squamous cell carcinomas of Indians.
TLDR
Analysis of exon 1beta of p14(ARF) gene of oral squamous cell carcinomas in untreated Indian patients revealed homozygous deletions in 14 of the 58 tumors; these results were confirmed by hybridization of tumor DNAs with ex on 1beta specific probe. Expand
Mutation of p16, p21 or cyclin dependent kinase 4 is rare in acute lymphoblastic leukaemia
TLDR
Results of this study showed mutation of p16, p21 or CDK4 to be rare events in Arab ALL patients. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 25 REFERENCES
Rates of p16 (MTS1) mutations in primary tumors with 9p loss.
TLDR
It is concluded that p16 is not the primary target of 9p21-22 loss in a large number of nonmelanoma primary tumors. Expand
Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers
TLDR
Polymerase chain reaction and Southern blot analysis confirmed the frequent deletion or rearrangement of the CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemias, and the absence of detectable gene transcripts. Expand
K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions.
TLDR
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. Expand
p53 mutations in pancreatic carcinoma and evidence of common involvement of homocopolymer tracts in DNA microdeletions.
TLDR
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. Expand
Mutations and altered expression of p16INK4 in human cancer.
TLDR
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. Expand
A cell cycle regulator potentially involved in genesis of many tumor types.
TLDR
Findings suggest that MTS1 mutations are involved in tumor formation in a wide range of tissues. Expand
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.
TLDR
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. Expand
Allelotype of pancreatic adenocarcinoma.
TLDR
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. Expand
Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes
TLDR
It is concluded that c-K-ras somatic mutational activation is a critical event in the oncogenesis of most, if not all, human cancers of the exocrine pancreas. Expand
Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes.
TLDR
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. Expand
...
1
2
3
...