CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer

Harriet Wikman (Corresponding Author), Penny Nymark, Aki Väyrynen, Sonata Jarmalaite, Anne Kallioniemi, Kaisa Salmenkivi, Katri Vainio-Siukola, Kirsti Husgafvel-Pursiainen, Sakari Knuutila, Maija Wolf, Sisko Anttila

Research output: Contribution to journalArticleScientificpeer-review

70 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)193 - 199
Number of pages7
JournalGenes, Chromosomes and Cancer
Volume42
Issue number2
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

Fingerprint

Lung Neoplasms
Genes
Neoplasms
Lung
Comparative Genomic Hybridization
Fluorescence In Situ Hybridization
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Gene Dosage
Oligonucleotide Array Sequence Analysis
Methylation
Carcinogenesis
Messenger RNA
Proteins

Cite this

Wikman, H., Nymark, P., Väyrynen, A., Jarmalaite, S., Kallioniemi, A., Salmenkivi, K., ... Anttila, S. (2005). CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer. Genes, Chromosomes and Cancer, 42(2), 193 - 199. https://doi.org/10.1002/gcc.20122
Wikman, Harriet ; Nymark, Penny ; Väyrynen, Aki ; Jarmalaite, Sonata ; Kallioniemi, Anne ; Salmenkivi, Kaisa ; Vainio-Siukola, Katri ; Husgafvel-Pursiainen, Kirsti ; Knuutila, Sakari ; Wolf, Maija ; Anttila, Sisko. / CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer. In: Genes, Chromosomes and Cancer. 2005 ; Vol. 42, No. 2. pp. 193 - 199.
@article{d92dca0d6aa440e0b804da170005c7f8,
title = "CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer",
abstract = "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.",
author = "Harriet Wikman and Penny Nymark and Aki V{\"a}yrynen and Sonata Jarmalaite and Anne Kallioniemi and Kaisa Salmenkivi and Katri Vainio-Siukola and Kirsti Husgafvel-Pursiainen and Sakari Knuutila and Maija Wolf and Sisko Anttila",
year = "2005",
doi = "10.1002/gcc.20122",
language = "English",
volume = "42",
pages = "193 -- 199",
journal = "Genes, Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "2",

}

Wikman, H, Nymark, P, Väyrynen, A, Jarmalaite, S, Kallioniemi, A, Salmenkivi, K, Vainio-Siukola, K, Husgafvel-Pursiainen, K, Knuutila, S, Wolf, M & Anttila, S 2005, 'CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer', Genes, Chromosomes and Cancer, vol. 42, no. 2, pp. 193 - 199. https://doi.org/10.1002/gcc.20122

CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer. / Wikman, Harriet (Corresponding Author); Nymark, Penny; Väyrynen, Aki; Jarmalaite, Sonata; Kallioniemi, Anne; Salmenkivi, Kaisa; Vainio-Siukola, Katri; Husgafvel-Pursiainen, Kirsti; Knuutila, Sakari; Wolf, Maija; Anttila, Sisko.

In: Genes, Chromosomes and Cancer, Vol. 42, No. 2, 2005, p. 193 - 199.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 42

SP - 193

EP - 199

JO - Genes, Chromosomes and Cancer

JF - Genes, Chromosomes and Cancer

SN - 1045-2257

IS - 2

ER -

Wikman H, Nymark P, Väyrynen A, Jarmalaite S, Kallioniemi A, Salmenkivi K et al. CDK4 is a probable target gene in a novel amplicon at 12q13.3–q14.1 in lung cancer. Genes, Chromosomes and Cancer. 2005;42(2):193 - 199. https://doi.org/10.1002/gcc.20122