Identification of chromosome arm 9p as the most frequent target of homozygous deletions in lung cancer.
Genome scanning at a 1-Mb resolution was undertaken in 29 lung cancer cell lines to clarify the distribution of homozygous (i.e., both allele) deletions along lung cancer genomes, using a high-resolution single nucleotide polymorphism array. Eighteen regions, including two known tumor suppressor loci, CDKN2A at 9p21 and FHIT at 3p14, were found homozygously deleted. Frequencies of deletions at the 18 regions were evaluated by genomic polymerase chain reaction in 78 lung cancer cell lines. Seven regions, 2q24, 3p14, 5q11, 9p21, 9p23, 11q14, and 21q21, were homozygously deleted in two or more cell lines. The CDKN2A locus at 9p21 was most frequently deleted (20/78, 26%), and the deletions were detected exclusively in non-small-cell lung carcinomas (NSCLCs). The PTPRD (protein tyrosine phosphatase receptor type D) locus at 9p23 was the second-most frequently deleted (8/78, 10%), and the deletions were detected in both small-cell lung carcinomas (SCLC) and NSCLC. In addition, the 9p24 region was deleted in a NSCLC. In total, 24 (31%) cell lines carried at least one deletion on chromosome arm 9p, while deletions on the remaining chromosome arms were observed at most in four (5%) cell lines. Deletions at 9p24, 9p23, and 9p21 were not contiguous with one another, and preferential co-occurrence or mutual exclusiveness for the deletions at these three loci was not observed. Thus, it was indicated that 9p is the most frequent target of homozygous deletions in lung cancer, suggesting that the arm contains multiple lung tumor suppressor genes and/or genomic features fragile during lung carcinogenesis.
Sato
Masamitsu
M
Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji, 5-chome, Chuo-ku, Tokyo, Japan.
Takahashi
Kenji
K
Nagayama
Kazuhiro
K
Arai
Yasuhito
Y
Ito
Nobue
N
Okada
Mitsumasa
M
Minna
John D
JD
Yokota
Jun
J
Kohno
Takashi
T
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D020133:Reverse Transcriptase Polymerase Chain Reaction
C090899:PTPRD protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2