Z. Piao et al., Identification of novel deletion regions on chromosome arms 2q and 6p in breast carcinomas by amplotype analysis, GENE CHROM, 30(2), 2001, pp. 113-122
DNA fingerprinting by arbitrarily primed PCR (AP-PCR) was employed to ident
ify molecular genetic alterations in 37 primary breast carcinomas. AP-PCR i
s a PCR-based technique that uses only one primer of arbitrary sequence tha
t generates a molecular karyotype (amplotype) of tumors. The breast cancer
amplotype generated with two arbitrary primers (MCGI and Blue) showed a rel
atively high frequency (more than 20% of the tumors) of gains at chromosome
s 1, 4, and 8, and of losses at chromosomes 2, 4, 6, 9, 10, 11, 13, and the
X chromosome. We further analyzed the regions most commonly gained at chro
mosome 8 (47%) and lost at chromosomes 2 (38%) and 6 (49%) by determining t
he subchromosomal localization of the fingerprint bands from these chromoso
mes. The region of gain at chromosome 8 was mapped at 8q24.1, close to MYC
Band MCGI-AI was assigned to chromosome band 2q22, and band Blue-J was assi
gned to 6p21. Common losses of these chromosomal regions have not been desc
ribed for breast cancer. To map these deletion regions more precisely, we p
erformed loss of hererozygosity (LOH) analysis by microallelotyping on 20 o
f the 37 cancers previously analyzed by AP-PCR and another additional 52 br
east carcinomas. The results suggest that the regions at 2q21-24 and 6p21-2
3 may harbor novel tumor suppressor genes for breast cancer. LOH at 2q21-24
(D2S2304) was more frequent in high-grade tumors (59%) than in low-grade r
umors (29) (P = 0.03). This suggests that this genetic alteration may be as
sociated with tumor progression and shows the power of the amplotype approa
ch in detecting novel genetic alterations that are useful as clinical param
eters of breast cancer. (C) 2001 Wiley-Liss, Inc.