At least five regions of imbalance on 6q in breast tumors, combining losses and gains

✍ Scribed by Carmen Rodriguez; Annick Causse; Elisabeth Ursule; Charles Theillet

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 266 KB
• Volume: 27
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(200001)27:1<76::aid-gcc10>3.0.co;2-e

✦ Synopsis

The long arm of chromosome 6 is frequently rearranged in human cancer. In breast cancer, allelotyping studies have indicated the existence of three to four distinct regions of allelic imbalance. Chromosome transfer studies have shown the presence of several growth inhibiting or senescence promoting genes in the segment between 6q13 and 6q27. Moreover, results from comparative genomic hybridization (CGH) analyses have indicated that 6q was indeed a site of chromosomal losses, but that it was also involved in a substantial number of gains. In the present work, we allelotyped 178 pairs of breast tumor and normal tissue DNAs using 30 CA repeat markers from the Genethon collection. Seventy-six percent of the tumors in our panel displayed allelic imbalance (AI) of at least one locus, but patterns of AI could be complex. Whereas 11 tumors showed AI at all markers tested, 57 presented zebra profiles, and 28 showed AI at one site only. We characterized five distinct domains of AI defined, from centromere to telomere, by D6S300 (domain 1), D6S434 (domain 2), D6S261 (domain 3), D6S314-D6S409 (domain 4), and D6S441-D6S415 (domain 5). Some of the domains could be narrowed down to intervals of 1cM or less. We performed CGH analysis on a subset of 34 tumors presenting AI of variable extent at 6q. In 10/34 tumors, CGH did not reveal any anomaly on 6q. Most of these presented AI on short intervals, thus being below the detection threshold by CGH. Of the remaining 24 tumors presenting anomalies by CGH, 11 presented gains involving all or portions of 6q and 15 losses (2 presented combined losses and gains). By CGH, the 6q21-22 region was most commonly involved in gains, whereas 6q13-14 and 6q25-27 were frequently lost. Thus, allelic imbalances on 6q can either represent a gain or a loss depending on the region involved.