BACKGROUND: The present study was planned to investigate cumulative genetic changes during development and progression of gallbladder carcinoma (GBC) in clinical patients. MATERIALS AND METHODS: We examined GBC DNA from resected tissue isolated from 56 cases of GBC for loss of heterozygosity (LOH) at six loci on five chromosomal arms (1p36, 9p21, 13q14, 16q24, 17p13), using highly polymorphic microsatellite markers. RESULTS: High incidences of LOH at 1p36 (19/36: 53%), 9p21 (12/32: 38%), 13q14 (20/36: 56%), 16q24 (31/54: 61%), and 17p13 (15/36: 42%) were detected. When comparing genetic features with clinicopathological stages of these tumors, it appeared that only LOH at 16q24 had a high incidence (5/6: 83%) at an early stage (T1a: tumor invades lamina propria) of the disease, although large numbers of LOH were found on all chromosomal arms in tumors of more advanced stages (T1b, T2, T3, and T4). CONCLUSION: These results suggested that the putative tumor suppressor gene on 16q24 may be strongly related to an early step of carcinogenesis in GBC and that GBC acquires a high malignant potential when the tumor invades the muscle layer. (c)2001 Elsevier Science.
BACKGROUND: The present study was planned to investigate cumulative genetic changes during development and progression of gallbladder carcinoma (GBC) in clinical patients. MATERIALS AND METHODS: We examined GBC DNA from resected tissue isolated from 56 cases of GBC for loss of heterozygosity (LOH) at six loci on five chromosomal arms (1p36, 9p21, 13q14, 16q24, 17p13), using highly polymorphic microsatellite markers. RESULTS: High incidences of LOH at 1p36 (19/36: 53%), 9p21 (12/32: 38%), 13q14 (20/36: 56%), 16q24 (31/54: 61%), and 17p13 (15/36: 42%) were detected. When comparing genetic features with clinicopathological stages of these tumors, it appeared that only LOH at 16q24 had a high incidence (5/6: 83%) at an early stage (T1a: tumor invades lamina propria) of the disease, although large numbers of LOH were found on all chromosomal arms in tumors of more advanced stages (T1b, T2, T3, and T4). CONCLUSION: These results suggested that the putative tumor suppressor gene on 16q24 may be strongly related to an early step of carcinogenesis in GBC and that GBC acquires a high malignant potential when the tumor invades the muscle layer. (c)2001 Elsevier Science.