Figure 3.
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.

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. Purple: gains; red: losses; green: neutral; gray: complex rearrangements.

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