TY - JOUR
T1 - CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer
AU - Wikman, Harriet
AU - Nymark, Penny
AU - Väyrynen, Aki
AU - Jarmalaite, Sonata
AU - Kallioniemi, Anne
AU - Salmenkivi, Kaisa
AU - Vainio-Siukola, Katri
AU - Husgafvel-Pursiainen, Kirsti
AU - Knuutila, Sakari
AU - Wolf, Maija
AU - Anttila, Sisko
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
U2 - 10.1002/gcc.20122
DO - 10.1002/gcc.20122
M3 - Article
SN - 1045-2257
VL - 42
SP - 193
EP - 199
JO - Genes, Chromosomes and Cancer
JF - Genes, Chromosomes and Cancer
IS - 2
ER -