Chromosomal changes in locally recurrent, hormone-refractory prostate carcinomas by karyotyping and comparative genomic hybridization.

The genetic mechanisms of prostate cancer recurrence during hormonal therapy are largely unknown. So far, data from conventional karyotype analysis on hormone-refractory prostate carcinomas have not been published, mainly because of the difficulties in obtaining fresh hormone-refractory prostate carcinoma samples and getting metaphases from them. Here, we have studied chromosomal changes in 12 locally recurrent, hormone-refractory prostate carcinomas using karyotyping and CGH that revealed genetic aberrations in all tumors. Loss of the Y chromosome was the most common (89%) finding, and tetraploidy or near-tetraploidy was detected in all tumors. Also non-random translocations were found in 56% of the tumors. The present study indicates that clonal chromosomal aberrations in hormone-refractory prostate carcinomas are more common than in untreated primary tumors, and also, further studies on the frequency and significance of translocations in prostate carcinoma progression during hormonal therapy are warranted.

A de novo deletion of chromosome 15(q15.2q21.2) in a dysmorphic, mentally retarded child with congenital scalp defect.

We report a rare chromosomal finding in a boy with a pronounced scalp defect, dysmorphic features and mental retardation. Initially, what seemed to be a normal karyotype by conventional karyotyping was determined to be a de novo deletion involving 15(q15.2q21.2) by high resolution banding. Consequently, prometaphase analysis is warranted in some cases when conventional karyotype analysis appears normal.

Apolipoprotein E genotype is not linked to locally recurrent hormone-refractory prostate cancer.

Mechanisms of prostate cancer recurrence during androgen deprivation are poorly understood. Recently, the putative role of apolipoprotein E varepsilon 4 allele in the aetiology of prostate cancer was raised. To investigate the hypothesis that varepsilon 4 allele of apolipoprotein E gene predisposes to prostate cancer and is involved in the relapse of hormonal therapy response, 38 hormone-refractory locally recurrent carcinoma samples from 38 prostate cancer patients were screened for apolipoprotein E genotype. The frequency distribution of apolipoprotein E genotypes among tumours did not differ significantly from that among controls. The allele frequency of varepsilon 4 was 19.7% and 19.3% in tumours and controls, respectively. The results suggest that clinical progression of prostate cancer during androgen withdrawal therapy is not associated with apolipoprotein E genotype. Prostate Cancer and Prostatic Diseases (2000) 3, 107-109

Trisomy 10p produced by recombination involving complex paternal translocation between chromosomes 1 and 10.

A complex and unique, apparently balanced translocation involving No. 1 long arm and No. 10 short and long arm, segregated in a family and produced an unbalanced progeny with recombination of t(10) translocation chromosome during paternal meiosis.

Androgen receptor alterations in prostate cancer relapsed during a combined androgen blockade by orchiectomy and bicalutamide.

Mechanisms of prostate cancer (CaP) recurrence during a combined androgen blockade (CAB) are poorly understood. Previously, the role of androgen receptor (AR) gene mutations underlying the CAB therapy relapse has been raised. To investigate the hypothesis that AR gene aberrations are involved in CAB relapse, 11 locally recurrent CaP samples from patients treated with orchiectomy and bicalutamide were analyzed for copy number changes and DNA sequence alterations of the AR gene by fluorescence in situ hybridization and single-strand conformation polymorphism, respectively. Altogether, base changes were detected in four tumors (36%). Three of them were missense mutations (G166S, W741C, M749I) and two were silent polymorphisms. Interestingly, none of the tumors had AR amplification. These data suggest that different AR variants are developed and selected for during various types of hormonal treatments, and also, that CAB achieved by orchiectomy and bicalutamide does not act as a selective force for AR amplification.

Mapping DNA sequences in a human X-chromosome deletion which extends across the region of the Duchenne muscular dystrophy mutation.

A somatic cell hybrid has been constructed and characterized using fibroblasts from a phenotypically normal woman who possesses an X chromosome with an interstitial deletion of the short arm. High-resolution banding indicates that the deleted segment is either Xp22.13-p11.4 or Xp22.11-p11.23. Southern blot hybridization to previously mapped DNA sequences confirms that the missing segment of the X chromosome is a deletion and not an interstitial translocation and supports the cytogenetic interpretation that the deletion extends proximal of Xp11.3 and therefore probably comprises Xp22.11-p11.23. Three further DNA sequences have been localized to the region of the deleted segment. The following order has been assigned to the seven probes used: Xpter-RC8-pXUT22-(OA1,C7,M2C)-L1.28-RD6 -Xcen.