Abstract
A putative tumor suppressor gene, p16 (MST1; multiple tumor suppressor 1/CDK4I; cyclin‐dependent kinase 4 inhibitor), was isolated and mapped on the short arm of chromosome 9 (9p). The significance of p16 mutations in gastric tumorigenesis was examined by assessing p16 mutations as well as loss of heterozygosity (LOH) on 9p in 13 gastric adenomas and 45 adenocarcinomas. LOH on 9p (IFNA; α‐interferon locus) was detected in 22% (5/23 informative cases) of differentiated adenocarcinomas, 10% (1/10) of undifferentiated carcinomas and none (0/6) of the adenomas. Although we found a sequence polymorphism at the second position of codon 99 (CGC/CAC) of the p16 in one gastric adenoma patient, no somatic mutations were detected in any of the gastric adenomas or adenocarcinomas. These results suggest that p16 mutations probably do not contribute to gastric tumorigenesis. However, these data suggest that another tumor suppressor gene on 9p (near the IFNA locus) may contribute to the progression of differentiated adenocarcinoma of the stomach
Keywords: Chromosome 9p, p16 gene, Gastric adenoma, Gastric adenocarcinoma
Full Text
The Full Text of this article is available as a PDF (174.1 KB).
REFERENCES
- 1).Olopade , O. I. , Bohlander , S. K. , Pomykala , H. , Maltepe , E. , Van Melle , E. , Le Beau , M. M. and Diaz , M. O.Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia . Genomics , 14 , 437 – 443 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 2).Fountain , J. W. , Karayiorgou , M. , Ernstoff , M. S. , Kirkwood , J. M. , Vlock , D. R. , Titus‐Ernstoff , L. , Bouchard , B. , Vijayasaradhi , S. , Houghton , A. N. , Lahti , J. , Kidd , V. J. , Housman , D. E. and Dracopoli , N. C.Homozygous deletions within human chromosome band 9p21 in melanoma . Proc. Natl. Acad. Sci. USA , 89 , 10557 – 10561 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3).Olopade , O. I. , Jenkins , R. B. , Ransom , D. T. , Malik , K. , Pomykala , H. , Nobori , T. , Cowan , J. M. , Rowley , J. D. and Diaz , M. O.Molecular analysis of deletions of the short arm of chromosome 9 in human gliomas . Cancer Res. , 52 , 2523 – 2529 ( 1992. ). [PubMed] [Google Scholar]
- 4).Olopade , O. I. , Buchhagen , D. L. , Malik , K. , Sherman , J. , Nobori , T. , Bader , S. , Nau , M. M. , Gazdar , A. F. , Minna , J. D. and Diaz , M. O.Homozygous loss of the interferon genes defines the critical region on 9p that is deleted in lung cancers . Cancer Res. , 53 , 2410 – 2415 ( 1993. ). [PubMed] [Google Scholar]
- 5).van der Riet , P. , Nawroz , H. , Hruban , R. H. , Corio , R. , Tokino , K. , Koch , W. and Sidransky , D.Frequent loss of chromosome 9p21–22 early in head and neck cancer progression . Cancer Res. , 54 , 1156 – 1158 ( 1994. ). [PubMed] [Google Scholar]
- 6).Kamb , A. , Gruis , N. A. , Weaver‐Feldhaus , J. , Liu , Q. , Harshman , K. , Tavtigian , S. V. , Stockert , E. , Day , R. S. , Johnson , B. E. and Skolnick , M. H.A cell cycle regulator potentially involved in genesis of many tumor types . Science , 264 , 436 – 440 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 7).Nobori , T. , Miura , K. , Wu , D. J. , Lois , A. , Takabayashi , K. and Carson , D. A.Deletions of the cyclin‐dependent kinase‐4 inhibitor gene in multiple human cancers . Nature , 368 , 753 – 756 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 8).Mori , T. , Miura , K. , Aoki , T. , Nishihira , T. , Mori , S. and Nakamura , Y.Frequent somatic mutation of the MTS1/CDK4I (multiple tumor suppressor/cyclin‐dependent kinase 4 inhibitor) gene in esophageal squamous cell carcinoma . Cancer Res. , 54 , 3396 – 3397 ( 1994. ). [PubMed] [Google Scholar]
- 9).Hollstein , M. , Sidransky , D. , Vogelstein , B. and Harris , C. C.p53 mutations in human cancers . Science , 253 , 49 – 53 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 10).Kwiatkowski , D. J. and Diaz , M. O.Dinucleotide repeat polymorphism at the IFNA locus (9p22) . Hum. Mol. Genet. , 1 , 658 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 11).Spruck , C. H. , Gonzalez‐Zulueta , M. , Shibata , A. , Simoneau , A. R. , Lin , M.‐F. , Gonzales , F. , Tsai , Y. C. and Jones , P. A.p16 gene in uncultured tumours . Nature , 370 , 183 – 184 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 12).Bonetta , L.Open questions on p16 . Nature , 370 , 180 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 13).Cairns , P. , Mao , L. , Merlo , A. , Lee , D. J. , Schwab , D. , Eby , Y. , Tokino , K. , van der Riet , P. , Blaugrund , J. E. and Sidransky , D.Rates of p16 (MTS1) mutations in primary tumors with 9p loss . Science , 265 , 415 – 416 ( 1994. ). [DOI] [PubMed] [Google Scholar]