Affordable Access

deepdyve-link
Publisher Website

Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.

Authors
  • Young, Richard J1
  • Waldeck, Kelly
  • Martin, Claire
  • Foo, Jung H
  • Cameron, Donald P
  • Kirby, Laura
  • Do, Hongdo
  • Mitchell, Catherine
  • Cullinane, Carleen
  • Liu, Wendy
  • Fox, Stephen B
  • Dutton-Regester, Ken
  • Hayward, Nicholas K
  • Jene, Nicholas
  • Dobrovic, Alexander
  • Pearson, Richard B
  • Christensen, James G
  • Randolph, Sophia
  • McArthur, Grant A
  • Sheppard, Karen E
  • 1 Research Division, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia. , (Australia)
Type
Published Article
Journal
Pigment Cell & Melanoma Research
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jul 01, 2014
Volume
27
Issue
4
Pages
590–600
Identifiers
DOI: 10.1111/pcmr.12228
PMID: 24495407
Source
Medline
Keywords
License
Unknown

Abstract

We have investigated the potential for the p16-cyclin D-CDK4/6-retinoblastoma protein pathway to be exploited as a therapeutic target in melanoma. In a cohort of 143 patients with primary invasive melanoma, we used fluorescence in situ hybridization to detect gene copy number variations (CNVs) in CDK4, CCND1, and CDKN2A and immunohistochemistry to determine protein expression. CNVs were common in melanoma, with gain of CDK4 or CCND1 in 37 and 18% of cases, respectively, and hemizygous or homozygous loss of CDKN2A in 56%. Three-quarters of all patients demonstrated a CNV in at least one of the three genes. The combination of CCND1 gain with either a gain of CDK4 and/or loss of CDKN2A was associated with poorer melanoma-specific survival. In 47 melanoma cell lines homozygous loss, methylation or mutation of CDKN2A gene or loss of protein (p16(INK) (4A) ) predicted sensitivity to the CDK4/6 inhibitor PD0332991, while RB1 loss predicted resistance.

Report this publication

Statistics

Seen <100 times