Deletion mapping of chromosome segment 11q24-q25, exhibiting extensive allelic loss in early onset breast cancer

Frequent allelic deletions at chromosome 11q24-q25 have been described in b oth early and late onset breast cancers, suggesting the existence of a gene locus implicated in the initiation and/or progression of the disease. In t he present study we fine mapped this region further by loss of heterozygosi ty (LOH) analysis in a population of early onset breast cancer cases (n = 1 02, 22 to 36 years old). Loss of chromosomal material was assessed for poss ible association with patient survival as well as Nottingham histologic gra de (NHG). Additionally, we investigated the involvement of the 11q24-q25 lo cus in a group of familiar breast cancer cases with no detectable BRCA1 or BRCA2 gene alterations (n 32, ages 28 to 40 years). Among the consecutive p atients, extensive LOH was observed for all markers at 11q24-q25, with freq uencies ranging from 42% to 54%. Deletion at the D11S4125 marker was found to be associated with reduced survival (p = 0.026), whereas the adjacent D1 1S387 marker correlated with higher histologic grade (p = 0.042). In the fa milial cases, the most telomeric markers showed substantially lower proport ions of LOH, ranging from 10% to 21%. Comparison of the two patient groups demonstrated that this difference in LOH frequency was statistically signif icant for the D11S4098, D11S968, D11S387 and D11IS4125 markers (p = 0.020, p = 0.029, p = 0.0090 and p = 0.0030, respectively). We conclude that 11q25 may harbor a gene implicated in early onset breast cancer, Our data sugges t that the most probable position for this locus is defined by the markers D11S387 and D11S4125 land furthermore that it may play a less significant r ole in familial breast cancer cases not linked to either of the BRCA genes. (C) 2001 Wiley-Liss, Inc.