BACKGROUND & AIMS: It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. METHODS: Fluorescence in situ hybridization (FISH) was performed on nuclei dissociated from sites of cancer, dysplasia, and UC-involved nondysplastic epithelium in five UC-related cancer colectomy specimens using a panel of pericentromeric probes. Comparative genomic hybridization (CGH) was used to detect clonal chromosomal losses and gains in DNA extracted from these sites. RESULTS: FISH analysis revealed significant and often dramatic alterations in chromosome copy number compared with controls in all biopsy specimens of cancer, dysplasia, and nondysplastic UC-involved epithelium. Clonal chromosomal losses and gains were detected by CGH in all but one analyzed site of dysplasia and cancer and in two of the five nondysplastic sites. FISH and CGH frequently detected the relative loss of chromosome 18. CONCLUSIONS: Chromosomal alterations may occur early in UC-related neoplastic progression and seem to precede the histological development of dysplasia. Relative loss of 18q may be important in the progression of UC-related neoplasia. The detection of chromosomal alterations as an intermediate end point may prove useful in identifying patients at high risk for the development of colorectal cancer.
BACKGROUND & AIMS: It is unclear whether genomic derangement precedes the histological development of dysplasia in ulcerative colitis (UC)-related neoplastic progression. The primary aim of this study was to determine if chromosomal alterations occur early in the progression pathway of UC-related neoplasia. METHODS: Fluorescence in situ hybridization (FISH) was performed on nuclei dissociated from sites of cancer, dysplasia, and UC-involved nondysplastic epithelium in five UC-related cancer colectomy specimens using a panel of pericentromeric probes. Comparative genomic hybridization (CGH) was used to detect clonal chromosomal losses and gains in DNA extracted from these sites. RESULTS: FISH analysis revealed significant and often dramatic alterations in chromosome copy number compared with controls in all biopsy specimens of cancer, dysplasia, and nondysplastic UC-involved epithelium. Clonal chromosomal losses and gains were detected by CGH in all but one analyzed site of dysplasia and cancer and in two of the five nondysplastic sites. FISH and CGH frequently detected the relative loss of chromosome 18. CONCLUSIONS: Chromosomal alterations may occur early in UC-related neoplastic progression and seem to precede the histological development of dysplasia. Relative loss of 18q may be important in the progression of UC-related neoplasia. The detection of chromosomal alterations as an intermediate end point may prove useful in identifying patients at high risk for the development of colorectal cancer.
Authors: Mary P Bronner; Jacintha N O'Sullivan; Peter S Rabinovitch; David A Crispin; Lu Chen; Mary J Emond; Cyrus E Rubin; Teresa A Brentnall Journal: Am J Pathol Date: 2008-11-06 Impact factor: 4.307
Authors: Mary P Bronner; Marek Skacel; David A Crispin; Peter D Hoff; Mary J Emond; Lisa A Lai; Raymond R Tubbs; Jacintha N O'Sullivan; Peter S Rabinovitch; Teresa A Brentnall Journal: Mod Pathol Date: 2010-08-27 Impact factor: 7.842
Authors: Teresa A Brentnall; Sheng Pan; Mary P Bronner; David A Crispin; Hamid Mirzaei; Kelly Cooke; Yasuko Tamura; Tatiana Nikolskaya; Lellean Jebailey; David R Goodlett; Martin McIntosh; Ruedi Aebersold; Peter S Rabinovitch; Ru Chen Journal: Proteomics Clin Appl Date: 2009-09-14 Impact factor: 3.494