Frequent homozygous deletions of the CDKN2A locus in somatic cancer tissues

Mutat Res. 2019 May:815:30-40. doi: 10.1016/j.mrfmmm.2019.04.002. Epub 2019 Apr 25.

Abstract

Here we present and describe data on homozygous deletions (HD) of human CDKN2 A and neighboring regions on the p arm of Chromosome 9 from cancer genome sequences deposited on the online Catalogue of Somatic Mutations in Cancer (COSMIC) database. Although CDKN2 A HDs have been previously described in many cancers, this is a pan-cancer report of these aberrations with the aim to map the distribution of the breakpoints. We find that HDs of this locus have a median range of 1,255,650bps. When the deletion breakpoints were mapped on both the telomere and centromere proximal sides of CDKN2A, most of the telomere proximal breakpoints concentrate to a narrow region of the chromosome which includes the gene MTAP.. The centromere proximal breakpoints of the deletions are distributed over a wider chromosomal region. Furthermore, gene expression analysis shows that the deletions that include the CDKN2A region also include the MTAP region and this observation is tissue independent. We propose a model that may explain the origin of the telomere proximal CDKN2A breakpoints Finally, we find that HD distributions for at least three other loci, RB1, SMAD4 and PTEN are also not random.

Keywords: CDKN2A; Homozygous deletion; Tumor suppressor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centromere / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 9 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Gene Deletion
  • Homozygote
  • Humans
  • Mutation / genetics*
  • Neoplasms / genetics*
  • Telomere / genetics
  • Tumor Cells, Cultured

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16