A catalog of genes homozygously deleted in human lung cancer and the candidacy of PTPRD as a tumor suppressor gene.
A total of 176 genes homozygously deleted in human lung cancer were identified by DNA array-based whole genome scanning of 52 lung cancer cell lines and subsequent genomic PCR in 74 cell lines, including the 52 cell lines scanned. One or more exons of these genes were homozygously deleted in one (1%) to 20 (27%) cell lines. These genes included known tumor suppressor genes, e.g., CDKN2A/p16, RB1, and SMAD4, and candidate tumor suppressor genes whose hemizygous or homozygous deletions were reported in several types of human cancers, such as FHIT, KEAP1, and LRP1B/LRP-DIP. CDKN2A/p16 and p14ARF located in 9p21 were most frequently deleted (20/74, 27%). The PTPRD gene was most frequently deleted (8/74, 11%) among genes mapping to regions other than 9p21. Somatic mutations, including a nonsense mutation, of the PTPRD gene were detected in 8/74 (11%) of cell lines and 4/95 (4%) of surgical specimens of lung cancer. Reduced PTPRD expression was observed in the majority (>80%) of cell lines and surgical specimens of lung cancer. Therefore, PTPRD is a candidate tumor suppressor gene in lung cancer. Microarray-based expression profiling of 19 lung cancer cell lines also indicated that some of the 176 genes, such as KANK and ADAMTS1, are preferentially inactivated by epigenetic alterations. Genetic/epigenetic as well as functional studies of these 176 genes will increase our understanding of molecular mechanisms behind lung carcinogenesis.
Kohno
Takashi
T
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Otsuka
Ayaka
A
Girard
Luc
L
Sato
Masanori
M
Iwakawa
Reika
R
Ogiwara
Hideaki
H
Sanchez-Cespedes
Montse
M
Minna
John D
JD
Yokota
Jun
J
D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015894:Genome, Human; D006720:Homozygote; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics*; D015203:Reproducibility of Results
C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2