PMID- 15900585 OWN - NLM STAT- MEDLINE DCOM- 20051121 LR - 20160303 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 117 IP - 2 DP - 2005 Nov 1 TI - Genomewide loss of heterozygosity and its clinical associations in non small cell lung cancer. PG - 241-7 AB - We extensively allelotyped a panel of 71 microdissected primary surgically resected non small cell lung cancer (NSCLC) tumors to identify chromosomal regions that are likely to contain tumor suppressor genes (TSGs) or associated with clinicopathologic and prognostic effects. Loss of heterozygosity (LOH) was detected by genotyping of 177 microsatellite markers and correlation of LOH with clinicopathologic parameters and prognosis was analyzed. Twenty markers showed an LOH frequency greater than 48%, and 8 of them (2p23.3, 2p24.3, 2q35, 6p22.2, 7p14.3, 7p22.2, 17q24.3 and 21q22.3) were novel in NSCLC. The high LOH regions were confirmed by further aligning continuous LOH regions from another set of 24 NSCLC tissues and defining 7 minimal deletion regions ranging from 1.29 to 12.26 cM. The aberrations of 8 markers showed a significant correlation with alteration of p16 and Rb proteins, suggesting the gene(s) located in the chromosomal loss that may interact with p16/Rb pathway. In addition, markers specifically associated with smoking, histology types and tumor stages were identified and the linked candidate TSGs were suggested. For example, marker D1S1612 closely linked with Mig-6 gene was associated with smoking patients, squamous cell carcinoma patients and late-stage patients. Furthermore, 3 markers, D2S2968, D6S2439 and D7S1818, were significantly associated with poor prognosis of NSCLC patients using both univariate and multivariate Cox's regression analyses (p = 0.035, 0.022 and 0.006, respectively). These markers can potentially be used for early lung cancer detection, outcome measurement and the positional cloning of new TSGs whose loss of function contributes to NSCLC tumorigenesis. FAU - Tseng, Ruo-Chia AU - Tseng RC AD - Department of Life Sciences, National Taiwan Normal University, Taipei, Taiwan. FAU - Chang, Jer-Wei AU - Chang JW FAU - Hsien, Feng-Jen AU - Hsien FJ FAU - Chang, Ya-Hui AU - Chang YH FAU - Hsiao, Chin-Fu AU - Hsiao CF FAU - Chen, Jung-Ta AU - Chen JT FAU - Chen, Chih-Yi AU - Chen CY FAU - Jou, Yuh-Shan AU - Jou YS FAU - Wang, Yi-Ching AU - Wang YC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Genetic Markers) SB - IM MH - Aged MH - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology MH - Chromosome Mapping MH - Female MH - Genetic Markers MH - *Genome, Human MH - Humans MH - *Loss of Heterozygosity MH - Lung Neoplasms/*genetics/mortality/pathology MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Survival Analysis EDAT- 2005/05/19 09:00 MHDA- 2005/12/13 09:00 CRDT- 2005/05/19 09:00 PHST- 2005/05/19 09:00 [pubmed] PHST- 2005/12/13 09:00 [medline] PHST- 2005/05/19 09:00 [entrez] AID - 10.1002/ijc.21178 [doi] PST - ppublish SO - Int J Cancer. 2005 Nov 1;117(2):241-7. doi: 10.1002/ijc.21178.