BACKGROUND: Microsatellite instability (MSI) and loss of heterozygosity (LOH) are lesions in the genome found with different frequencies in gastric carcinomas (GCAs). Despite a great body of studies, no systematic approach to the detailed classification of MSI and LOH in the two major types of GCA has been published. METHODS: Thirty-seven advanced GCAs, 25 intestinal-type (IGCAs) and 12 diffuse-type (DGCAs), were assayed with 15 autosomal tetranucleotide markers on 14 chromosomal arms. The observed frequencies and types of microsatellite alterations allowed stratification into subgroups, i.e., high- and low-grade MSI (MSI-H, MSI-L) or microsatellite-stable (MSS), and high- or low-grade, or non-detectable LOH (LOH-H, LOH-L, LOH-N). RESULTS: Collectively, the markers detected MSI-H tumors with sensitivity equal to that of BAT-26 (a single marker highly specific for MSI-H). Likewise, the markers detected LOH at chromosomal arms 5q, 18q, and 21q with a sensitivity equal to markers used previously. Seven (19%) MSI-H and six (16%) LOH-H tumors were found, with a significant association (P = 0.027) with IGCA: 92% of MSI-H and LOH-H occurred in IGCA patients only. Conversely, in DGCA, a significantly higher prevalence of a stable (LOH-N/MSS) phenotype was found as compared with IGCA (75.1% vs 28.0%; P = 0.035). The MSI-L phenotype was found in 57.9% of non-MSI-H IGCA tumors and was associated significantly (P = 0.015) with LOH-H. CONCLUSION: A clear difference in genomic instability between IGCA and DGCA was found. In IGCA, the MSI and LOH pathways were more commonly involved, whereas in DGCA, a stable phenotype was predominant. As a novel finding, MSI-L as a true phenomenon and its association with LOH was observed in IGCA.
BACKGROUND: Microsatellite instability (MSI) and loss of heterozygosity (LOH) are lesions in the genome found with different frequencies in gastric carcinomas (GCAs). Despite a great body of studies, no systematic approach to the detailed classification of MSI and LOH in the two major types of GCA has been published. METHODS: Thirty-seven advanced GCAs, 25 intestinal-type (IGCAs) and 12 diffuse-type (DGCAs), were assayed with 15 autosomal tetranucleotide markers on 14 chromosomal arms. The observed frequencies and types of microsatellite alterations allowed stratification into subgroups, i.e., high- and low-grade MSI (MSI-H, MSI-L) or microsatellite-stable (MSS), and high- or low-grade, or non-detectable LOH (LOH-H, LOH-L, LOH-N). RESULTS: Collectively, the markers detected MSI-H tumors with sensitivity equal to that of BAT-26 (a single marker highly specific for MSI-H). Likewise, the markers detected LOH at chromosomal arms 5q, 18q, and 21q with a sensitivity equal to markers used previously. Seven (19%) MSI-H and six (16%) LOH-H tumors were found, with a significant association (P = 0.027) with IGCA: 92% of MSI-H and LOH-H occurred in IGCA patients only. Conversely, in DGCA, a significantly higher prevalence of a stable (LOH-N/MSS) phenotype was found as compared with IGCA (75.1% vs 28.0%; P = 0.035). The MSI-L phenotype was found in 57.9% of non-MSI-H IGCA tumors and was associated significantly (P = 0.015) with LOH-H. CONCLUSION: A clear difference in genomic instability between IGCA and DGCA was found. In IGCA, the MSI and LOH pathways were more commonly involved, whereas in DGCA, a stable phenotype was predominant. As a novel finding, MSI-L as a true phenomenon and its association with LOH was observed in IGCA.
Authors: Asta Varis; Maija Wolf; Outi Monni; Marja-Leena Vakkari; Arto Kokkola; Chris Moskaluk; Henry Frierson; Steven M Powell; Sakari Knuutila; Anne Kallioniemi; Wa'el El-Rifai Journal: Cancer Res Date: 2002-05-01 Impact factor: 12.701
Authors: Alex Duval; Maryline Reperant; Aurore Compoint; Raquel Seruca; Guglielmina N Ranzani; Barry Iacopetta; Richard Hamelin Journal: Cancer Res Date: 2002-03-15 Impact factor: 12.701
Authors: Sarah E R Halford; Elinor J Sawyer; Maryou B Lambros; Patricia Gorman; Nicola D Macdonald; Ian C Talbot; William D Foulkes; Cheryl E Gillett; Diana M Barnes; Lars A Akslen; Kwok Lee; Ian J Jacobs; Andrew M Hanby; Trivadi S Ganesan; Helga B Salvesen; Walter F Bodmer; Ian P M Tomlinson; Rebecca R Roylance Journal: J Pathol Date: 2003-11 Impact factor: 7.996
Authors: A Gylling; W M Abdel-Rahman; M Juhola; K Nuorva; E Hautala; H J Järvinen; J-P Mecklin; M Aarnio; P Peltomäki Journal: Gut Date: 2007-01-31 Impact factor: 23.059