Figure 3.
Clustering of somatic chromosomal rearrangements in FA patients at the MHC locus (6p21) and chromosome arms 1q and 3q. (A) Out of 51 CMEs in FA patients, 5 (9.8%) had breakpoints within or near the MHC–HLA locus at 6p21 (P = 7.3 × 10−9 [2 terminal 6p losses in FA351 and FA072, 2 terminal 6p UPD in FA013 and FA106, and an interstitial gain in FA013]), suggesting that this region is a hotspot for somatic chromosomal rearrangements. Dashed lines delimitate the CIs for the specific breakpoints, spanning as much as 11 Mb in 6p UPD in FA013. (B) A total of 6 CMEs (11.7%) involved 3q in 5 FA individuals (EGF058, FA072, FA178, FA351, and FA647), all of them genomic gains. (C) Five additional gain-type CMEs (9.8%) in 5 individuals (FA072, 041869_b; FA648; EGF058; FA360) were located in 1q as shown. The plots, generated with the University of California, Santa Cruz genomic browser (http://genome.ucsc.edu/), show the distribution of rearrangements in FA patients along with those previously reported in the population, based on multiple case-control studies of cancer.7 Purple: gains; red: losses; green: neutral; gray: complex rearrangements.