Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia

Citation
Tkh. Chung et al., Loss of heterozygosity at the short arm of chromosome 3 in microdissected cervical intraepithelial neoplasia, CANCER LETT, 154(2), 2000, pp. 189-194
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CANCER LETTERS
ISSN journal
0304-3835 → ACNP
Volume
154
Issue
2
Year of publication
2000
Pages
189 - 194
Database
ISI
SICI code
0304-3835(20000630)154:2<189:LOHATS>2.0.ZU;2-I
Abstract
Loss of heterozygosity (LOH) is a common genetic finding in many human neop lasms, including cervical cancer. The detection of LOH at specific loci in the precursor of cervical cancer, cervical intraepithelial neoplasia (CIN) may help in elucidating the evolution of this cancer, which has a clearly d efined histological premalignant phase. However, molecular genetic investig ation of CIN is difficult because many of the lesions are very small and so metimes ill defined topographically. In this study we analyzed eighteen pol ymorphic microsatellite repeats on chromosome 3p in CINs using a method of primer extension pre-amplification (PEP) for whole genome amplification com bined with microdissection. These markers encompass chromosome region 3pter -3p12. LON at one or more loci was detected in five (33%) out of the 15 inf ormative cases with low grade CIN (CIN 1), while 22 (92%) out of 24 cases w ith high grade CIN (CIN 2 and 3) (P < 0.01). The highest incidence (41%) of LOH was detected at locus D3S1038 (3p26.1-3p25.2). Frequent LOH (more than 20%) was also found at other loci including D3S1110 (3p35.3-3p25.1) (31%), D3S656 (3p25.1) (24%), D3S1076 (3p21.2-3p21.1) (29%), D3S1300 (3p21.1-3p14 .2) (24%), D3S1600 (3p14.2-3p14.1) (24%), and D3S1079 (3p13) (25%). The res ults from this study taken together with others indicate that the genetic a lterations on chromosome 3p are common in high grade of CIN and are probabl y early events in cervical carcinogenesis. Tumor suppressor gene(s) that pl ay a role in cervical neoplasm may be located on the short arm of chromosom e 3, likely at or near 3p26.1-25.1, 3p21.2-21.1, and 3p14.2-13. (C) 2000 El sevier Science Ireland Ltd, All rights reserved.