Androgen receptor gene methylation and exon one CAG repeat length in ovarian cancer: Differences from breast cancer

Kassim, S., Zoheiry, N., Hamed, W., Going, J. and Craft, J. (2004) Androgen receptor gene methylation and exon one CAG repeat length in ovarian cancer: Differences from breast cancer. IUBMB Life, 56(7), pp. 417-426. (doi: 10.1080/1521654040008952)

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More than one neoplastic founder clone can exist in benign epithelial tumours. Although theories of clonal selection make pluriclonality appear unlikely in carcinomas, published data do not exclude this possibility. This study looked for evidence of multiclonal X inactivation in ovarian carcinoma using AR methylation as a marker. Fifteen unifocal ovarian carcinomas and 14 multifocal carcinomas all in Scottish patients were studied. One representative formalin-fixed paraffin-embedded tumour block was chosen for each of the former and two for the latter. From each of these 43 tumour blocks three samples each of similar to 10(4) carcinoma cells were obtained by microdissection ( 129 in all). DNA released by proteinase K digestion was subjected to PCR amplification of the androgen receptor gene AR exon I CAG repeat polymorphism with and without prior digestion with methylation-sensitive restriction enzymes HpaII and HhaI. Complex amplification patterns were consistent with mosaic X inactivation in some ovarian carcinomas but acquired anomalies of AR methylation cannot be excluded. Parallel analysis of other X-linked polymorphic loci would strengthen the inference of clonality status from DNA methylation data in tumour X studies. Strikingly, the number of CAG repeats in the 29 ovarian tumour patients ( median 16, range 11 - 20) was substantially fewer than in 34 previously studied breast cancer patients from the same scottish population (median 21, range 14 - 26; P<0.0001), and women homozygous for the AR CAG repeat were over-represented in the ovarian cancer patients but not in the breast cancer series. These findings reinforce recent suggestions that AR may have a role in ovarian carcinogenesis.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Going, Dr James
Authors: Kassim, S., Zoheiry, N., Hamed, W., Going, J., and Craft, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:IUBMB Life

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