Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Feb;73(3):344–348. doi: 10.1038/bjc.1996.59

Mutational analysis of the CDKN2 gene in metastases from patients with cutaneous malignant melanoma.

A Platz 1, U Ringborg 1, B Lagerlöf 1, E Lundqvist 1, P Sevigny 1, M Inganäs 1
PMCID: PMC2074427  PMID: 8562340

Abstract

We analysed 26 metastases from 25 patients with sporadic cutaneous malignant melanoma for alterations in the CDKN2 gene by a combined polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP)/nucleotide sequencing approach. Eleven alterations (one in exon 1, five in exon 2 and five in the 3' non-coding sequence of the exon 3 region) were concordantly and independently detected by both SSCP and nucleotide sequence analysis. Two of the exon 2 changes and the five changes in the non-coding exon 3 region are likely to represent natural polymorphism. Four (15%) of 26 metastases thus had CDKN2 mutations and belonged to 3 (12%) of 25 patients. Semi-quantitative PCR furthermore revealed no sign of homozygous deletions of the CDKN2 exon 2 region. The results support an involvement of the CDKN2 product in the development of a subgroup of sporadic melanomas and encourage the search for alterations in additional genes of the 9p21 region.

Full text

PDF
344

Images in this article

345Figure 1
on p.345
346Figure 2
on p.346

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cairns P., Mao L., Merlo A., Lee D. J., Schwab D., Eby Y., Tokino K., van der Riet P., Blaugrund J. E., Sidransky D. Rates of p16 (MTS1) mutations in primary tumors with 9p loss. Science. 1994 Jul 15;265(5170):415–417. doi: 10.1126/science.8023167. [DOI] [PubMed] [Google Scholar]
  2. Caldas C., Hahn S. A., da Costa L. T., Redston M. S., Schutte M., Seymour A. B., Weinstein C. L., Hruban R. H., Yeo C. J., Kern S. E. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet. 1994 Sep;8(1):27–32. doi: 10.1038/ng0994-27. [DOI] [PubMed] [Google Scholar]
  3. Cannon-Albright L. A., Goldgar D. E., Meyer L. J., Lewis C. M., Anderson D. E., Fountain J. W., Hegi M. E., Wiseman R. W., Petty E. M., Bale A. E. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science. 1992 Nov 13;258(5085):1148–1152. doi: 10.1126/science.1439824. [DOI] [PubMed] [Google Scholar]
  4. Goldstein A. M., Dracopoli N. C., Ho E. C., Fraser M. C., Kearns K. S., Bale S. J., McBride O. W., Clark W. H., Jr, Tucker M. A. Further evidence for a locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) on chromosome 1p, and evidence for genetic heterogeneity. Am J Hum Genet. 1993 Mar;52(3):537–550. [PMC free article] [PubMed] [Google Scholar]
  5. Greene M. H., Clark W. H., Jr, Tucker M. A., Kraemer K. H., Elder D. E., Fraser M. C. High risk of malignant melanoma in melanoma-prone families with dysplastic nevi. Ann Intern Med. 1985 Apr;102(4):458–465. doi: 10.7326/0003-4819-102-4-458. [DOI] [PubMed] [Google Scholar]
  6. Gruis N. A., Weaver-Feldhaus J., Liu Q., Frye C., Eeles R., Orlow I., Lacombe L., Ponce-Castaneda V., Lianes P., Latres E. Genetic evidence in melanoma and bladder cancers that p16 and p53 function in separate pathways of tumor suppression. Am J Pathol. 1995 May;146(5):1199–1206. [PMC free article] [PubMed] [Google Scholar]
  7. Hannon G. J., Beach D. p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature. 1994 Sep 15;371(6494):257–261. doi: 10.1038/371257a0. [DOI] [PubMed] [Google Scholar]
  8. Kamb A., Gruis N. A., Weaver-Feldhaus J., Liu Q., Harshman K., Tavtigian S. V., Stockert E., Day R. S., 3rd, Johnson B. E., Skolnick M. H. A cell cycle regulator potentially involved in genesis of many tumor types. Science. 1994 Apr 15;264(5157):436–440. doi: 10.1126/science.8153634. [DOI] [PubMed] [Google Scholar]
  9. Lagerkvist A., Stewart J., Lagerström-Fermér M., Landegren U. Manifold sequencing: efficient processing of large sets of sequencing reactions. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2245–2249. doi: 10.1073/pnas.91.6.2245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mori T., Miura K., Aoki T., Nishihira T., Mori S., 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. 1994 Jul 1;54(13):3396–3397. [PubMed] [Google Scholar]
  11. Nobori T., Miura K., Wu D. J., Lois A., Takabayashi K., Carson D. A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21;368(6473):753–756. doi: 10.1038/368753a0. [DOI] [PubMed] [Google Scholar]
  12. Ohta M., Nagai H., Shimizu M., Rasio D., Berd D., Mastrangelo M., Singh A. D., Shields J. A., Shields C. L., Croce C. M. Rarity of somatic and germline mutations of the cyclin-dependent kinase 4 inhibitor gene, CDK4I, in melanoma. Cancer Res. 1994 Oct 15;54(20):5269–5272. [PubMed] [Google Scholar]
  13. Okamoto A., Demetrick D. J., Spillare E. A., Hagiwara K., Hussain S. P., Bennett W. P., Forrester K., Gerwin B., Serrano M., Beach D. H. Mutations and altered expression of p16INK4 in human cancer. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11045–11049. doi: 10.1073/pnas.91.23.11045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Serrano M., Hannon G. J., Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4. Nature. 1993 Dec 16;366(6456):704–707. doi: 10.1038/366704a0. [DOI] [PubMed] [Google Scholar]
  15. Spruck C. H., 3rd, Gonzalez-Zulueta M., Shibata A., Simoneau A. R., Lin M. F., Gonzales F., Tsai Y. C., Jones P. A. p16 gene in uncultured tumours. Nature. 1994 Jul 21;370(6486):183–184. doi: 10.1038/370183a0. [DOI] [PubMed] [Google Scholar]
  16. Vincent S., Marty L., Fort P. S26 ribosomal protein RNA: an invariant control for gene regulation experiments in eucaryotic cells and tissues. Nucleic Acids Res. 1993 Mar 25;21(6):1498–1498. doi: 10.1093/nar/21.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Xu L., Sgroi D., Sterner C. J., Beauchamp R. L., Pinney D. M., Keel S., Ueki K., Rutter J. L., Buckler A. J., Louis D. N. Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas. Cancer Res. 1994 Oct 15;54(20):5262–5264. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES