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CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer
Author(s) -
Wikman Harriet,
Nymark Penny,
Väyrynen Aki,
Jarmalaite Sonata,
Kallioniemi Anne,
Salmenkivi Kaisa,
VainioSiukola Katri,
HusgafvelPursiainen Kirsti,
Knuutila Sakari,
Wolf Maija,
Anttila Sisko
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20122
Subject(s) - amplicon , cdkn2a , biology , fluorescence in situ hybridization , tissue microarray , lung cancer , gene duplication , comparative genomic hybridization , cancer research , immunohistochemistry , microbiology and biotechnology , gene , cancer , cyclin d1 , tumor progression , copy number variation , pathology , polymerase chain reaction , genetics , cell cycle , medicine , genome , chromosome , immunology
Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1–CCND1–CDKN2A pathway, involved in the G1–S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3–q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10–15 genes with the most consistent amplifications. Semiquantitative RT‐PCR analyses of 13 genes in this region showed that four of them ( CDK4 , CYP27B1 , METTL1 , and TSFM ) were also highly up‐regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression ( n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3–q14.1 amplification. For CDK4 , a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT‐PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1–CCND1 pathway in lung tumorigenesis. © 2004 Wiley‐Liss, Inc.