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
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.