TY - JOUR
T1 - Intratumor heterogeneity of chromosome 1, 7, 17, and 18 aneusomies obtained by FISH and association with flow cytometric DNA index in human colorectal adenocarcinomas
AU - Di Vinci, Agela
AU - Infusini, Edmondo
AU - Peveri, Consuelo
AU - Sciutto, Andrea
AU - Orecchia, Roberto
AU - Geido, Elio
AU - Monaco, Roberto
AU - Giaretti, Walter
PY - 1999/4/1
Y1 - 1999/4/1
N2 - Background: The origin and evolution of somatic chromosome aberrations in colorectal cancer is still poorly understood. That data in the literature suggest that some specific chromosome aberrations are more common. It is not known, however, if there is a correlation of these with near-diploid and high aneuploidy previously proposed to be a characteristic of the adenoma- carcinoma sequence. Methods: Chromosome 1, 7, 17 and 18 numerical aberrations and 1p deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correlated with flow cytometric DNA index (DI) values. Results: Aneusomy for at least one of the investigated chromosomes was observed in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (95%). Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intratumor homogenous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogenous. Aneusomies of chromosomes 1, 7, and 17 were strongly associated with DNA high aneuploidy (DI ≥ 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common among DNA diploid and near-diploid tumors (DI <1.4 DI ≠ 1). Conclusions: Overall, these data suggest the existence of different aneuploidization routes correlated with specific chromosome aberrations. In addition, intratumor homogeneity of 1p deletions appears to be an indication of early occurrence or strong selection. We also suggest that tumors with monosomies and in particular monosomies-trisomies for the same chromosomes support a model of aneuploidization and chromosomes instability during the colorectal tumor progression based on loss of symmetry during chromosome segregation (Giaretti: Lab Invest 71:904-910, 1994).
AB - Background: The origin and evolution of somatic chromosome aberrations in colorectal cancer is still poorly understood. That data in the literature suggest that some specific chromosome aberrations are more common. It is not known, however, if there is a correlation of these with near-diploid and high aneuploidy previously proposed to be a characteristic of the adenoma- carcinoma sequence. Methods: Chromosome 1, 7, 17 and 18 numerical aberrations and 1p deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correlated with flow cytometric DNA index (DI) values. Results: Aneusomy for at least one of the investigated chromosomes was observed in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (95%). Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intratumor homogenous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogenous. Aneusomies of chromosomes 1, 7, and 17 were strongly associated with DNA high aneuploidy (DI ≥ 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common among DNA diploid and near-diploid tumors (DI <1.4 DI ≠ 1). Conclusions: Overall, these data suggest the existence of different aneuploidization routes correlated with specific chromosome aberrations. In addition, intratumor homogeneity of 1p deletions appears to be an indication of early occurrence or strong selection. We also suggest that tumors with monosomies and in particular monosomies-trisomies for the same chromosomes support a model of aneuploidization and chromosomes instability during the colorectal tumor progression based on loss of symmetry during chromosome segregation (Giaretti: Lab Invest 71:904-910, 1994).
KW - 1p deletions
KW - Colorectal carcinomas
KW - DNA flow cytometry
KW - Interphase FISH
KW - Numerical chromosome aberrations
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U2 - 10.1002/(SICI)1097-0320(19990401)35:4<369::AID-CYTO10>3.0.CO;2-6
DO - 10.1002/(SICI)1097-0320(19990401)35:4<369::AID-CYTO10>3.0.CO;2-6
M3 - Article
C2 - 10213203
AN - SCOPUS:0033119762
VL - 35
SP - 369
EP - 375
JO - Cytometry Part B - Clinical Cytometry
JF - Cytometry Part B - Clinical Cytometry
SN - 1552-4949
IS - 4
ER -