Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic event in early stages of non-small cell lung cancer.
Chromosomal imbalances resulting in altered gene dosage play a role in the molecular pathogenesis of non-small cell lung cancer (NSCLC), but the target genes remain to be identified. To identify early-stage genetic events that drive progression of NSCLC, we conducted a high-resolution array comparative genomic hybridization (CGH) study, using an array of 4,046 bacterial artificial chromosome clones to screen for DNA copy number changes associated with individual genes in 36 tumors obtained from patients in early stages of NSCLC. Multiple early genetic events occurring on chromosome 5p were identified, with a minimal detection region at 5p15.33 approximately 12. The most frequent finding involved gain of 5p15.33, observed in 15 of 19 stage I (A+B) cancers (79%) and in 28 of the total 36 NSCLC cases (78%). This locus harbors the genes TERT, SLC6A19, and SLC6A18 and is a telomeric boundary at bacterial artificial chromosome (BAC) clone 91_J20. Other potential candidate genes evidencing high numbers of genomic copy number changes (> or =40% of patients) included the following genes, encountered in >50% of 19 stage I (A+B) cancers: CEP72 and TPPP (14 of 19; 74%); AHRR, EXOC3 (previously SEC6L1), SLC9A3, LOC442126, ZDHHC11, BRD9, and TRIP13 (13/19; 68%); and CLPTM1L (alias CRR9), SLC6A3 (previously DAT1), and LOC401169 (10/19; 53%). Fluorescence in situ hybridization validated the array CGH findings. The gain of 5p15.33 is thus one of the most consistent alterations in the early stages of lung cancer, and a series of genes in the critical 5p15.33 region may be used as novel biomarkers for the early detection and classification of lung cancer.
Kang
Ji Un
JU
Department of Laboratory Medicine, Chungnam National University Hospital, Daesa-dong 640, Taejeon City 301-721, Korea.
Koo
Sun Hoe
SH
Kwon
Kye Chul
KC
Park
Jong Woo
JW
Kim
Jin Man
JM
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002869:Chromosome Aberrations; D022202:Chromosomes, Artificial, Bacterial; D002895:Chromosomes, Human, Pair 5; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis; D019098:Telomerase / Q000235:genetics
C509186:TERT protein, human; D019098:Telomerase