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Intratumor chromosomal heterogeneity in advanced carcinomas of the uterine cervix
- Source :
- International Journal of Cancer. 111:358-366
- Publication Year :
- 2004
- Publisher :
- Wiley, 2004.
-
Abstract
- Intratumor heterogeneity in chromosomal aberrations is believed to represent a major challenge in the treatment of cancer. The aim of our work was to assess the chromosomal heterogeneity of advanced cervical carcinomas and to distinguish aberrations that had occurred at a late stage of the disease from early events. A total of 55 biopsies, sampled from 2–4 different sites within 20 tumors, were analyzed by use of comparative genomic hybridization. Heterogeneous aberrations were identified as those present in at least 1 of the biopsies and which were not seen, nor seen as a tendency, in the others of the same tumor. The homogeneous aberrations were those seen in all biopsies of the tumor. The most frequent homogeneous aberrations were gain of 3q (65%), 20q (65%) and 5p (50%), indicating that these are early events in the development of the disease. Chromosomal heterogeneity was observed in 11 tumors. The most frequent heterogeneous aberrations were loss of 4p14–q25 (60% of 10 cases with this aberration), and gain of 2p22–pter (50% of 6 cases), 11qcen–q13 (33% of 9 cases) and 8q (27% of 11 cases), suggesting that these events promote progression at a later stage. Many of the heterogeneous regions contained genes known to influence the prognosis of cervical cancer, such as 7p (EGFR), 8q (c-MYC), 11qcen-q13 (CCND1) and 17q (ERBB2). Three evolution sequences for the subpopulations in the heterogeneous tumors were identified: a serial, a parallel and a mixed sequence. In 2 tumors with a serial sequence, it was indicated that the aberrations +8 and −X had occurred after the other heterogeneous aberrations and hence were the aberrations most recently formed. Our results suggest pronounced chromosomal instability in advanced cervical carcinomas. Moreover, aggressive and treatment-resistant subpopulations may emerge at a late stage and possibly contribute to a poor prognosis of the advanced stages. © 2004 Wiley-Liss, Inc.
Details
- ISSN :
- 00207136
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- International Journal of Cancer
- Accession number :
- edsair.doi...........b3e92ff593d954de34d9a32d901b4250
- Full Text :
- https://doi.org/10.1002/ijc.20258