PMID- 15361122 OWN - NLM STAT- MEDLINE DCOM- 20050224 LR - 20101118 IS - 0001-2815 (Print) IS - 0001-2815 (Linking) VI - 64 IP - 4 DP - 2004 Oct TI - High level of chromosome 15 aneuploidy in head and neck squamous cell carcinoma lesions identified by FISH analysis: limited value of beta2-microglobulin LOH analysis. PG - 452-61 AB - In cancer research, loss of heterozygosity (LOH), defined by microsatellite markers, is frequently used in the identification of gene loss. Especially, genomic alterations in the human leukocyte antigen (HLA) genes and the beta2-microglobulin (beta2m) gene on chromosome 15 are of interest regarding their function in the immune system. Because LOH analysis detects any allelic imbalance and not just allelic loss, we evaluated the LOH analysis in 11 head and neck squamous cell carcinoma (HNSCC) lesions using fluorescence in situ hybridization (FISH). The 11 tumors were selected out of 53 HNSCC lesions based upon beta2m LOH analysis and beta2m expression. Centromere 1 and 15 FISH were developed to determine the chromosome 15 copy number. Sequence-based mutation analysis of beta2m was conducted on tumors without beta2m expression; no mutations in the coding sequences were found. For five HNSCC lesions with LOH and beta2m expression, centromere 15 FISH indicated gain rather than loss. In the majority of the 11 HNSCC lesions, FISH showed centromere 1 and 15 heterogeneity throughout the tumor. Moreover, FISH indicated a more complex chromosome 1 and 15 distribution than could be concluded from microsatellite LOH analysis. Our results show that microsatellite LOH analysis does not represent the beta2m gene copy number and support the results obtained from comparative genomic hybridization (CGH) studies. Conclusions on genomic alterations in tumors cannot be based on LOH data only but depend on the results of immunohistochemical staining, FISH, and CGH. FAU - Koene, G J P A AU - Koene GJ AD - Department of Pathology, University Medical Center, Utrecht, The Netherlands. FAU - Arts-Hilkes, Y H A AU - Arts-Hilkes YH FAU - van der Ven, K J W AU - van der Ven KJ FAU - Rozemuller, E H AU - Rozemuller EH FAU - Slootweg, P J AU - Slootweg PJ FAU - de Weger, R A AU - de Weger RA FAU - Tilanus, M G J AU - Tilanus MG LA - eng PT - Journal Article PL - England TA - Tissue Antigens JT - Tissue antigens JID - 0331072 RN - 0 (beta 2-Microglobulin) SB - IM MH - Allelic Imbalance/genetics MH - Carcinoma, Squamous Cell/*genetics/pathology MH - Chromosomes, Human, Pair 1/genetics MH - Chromosomes, Human, Pair 15/*genetics MH - Genetic Linkage MH - Head and Neck Neoplasms/*genetics/pathology MH - Humans MH - In Situ Hybridization, Fluorescence MH - Loss of Heterozygosity/*genetics MH - beta 2-Microglobulin/*genetics EDAT- 2004/09/14 05:00 MHDA- 2005/02/25 09:00 CRDT- 2004/09/14 05:00 PHST- 2004/09/14 05:00 [pubmed] PHST- 2005/02/25 09:00 [medline] PHST- 2004/09/14 05:00 [entrez] AID - TAN291 [pii] AID - 10.1111/j.1399-0039.2004.00291.x [doi] PST - ppublish SO - Tissue Antigens. 2004 Oct;64(4):452-61. doi: 10.1111/j.1399-0039.2004.00291.x.