Follicular lymphoma with a novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells

Telomere healing following DNA polymerase arrest-induced breakages is likely the main mechanism generating chromosome 4p terminal deletions

“…These repeats mediate a process of nonhomologous recombination that introduces variation in the constant region of an immunoglobulin heavy chain gene. Those switch repeats have been noted at translocation breakpoints associated with a number of hematological malignancies [Fenton et al, 2002]. Moreover, repeat 5 was also shown to be significantly overrepresented within close proximity at translocation breakpoints (p=0.05) [Abeysinghe et al, 2003].…”

Lymphoma stem cells: enough evidence to support their existence?

“…Lastly, rare cases of FL display CSR-related BCL2-IGH rearrangements, indicating a late germinal center origin. 43 Importantly, in FL and in some germinal center-derived DLBCL cells, the presence of intraclonal IGH nucleotide variation indicates that the translocation t(14;18)(q32;q21) must have occurred in pre-germinal or early germinal center B lymphocytes (possibly centroblasts in the dark zone of the germinal center), after which divergences in the SHM and CSR processes gave rise to different clones with heterogeneous IG sequences and multiple isotype transcripts. 44,45 Moreover, these lymphomas usually present variation in the pattern of IG hypermutation during disease progression.…”

AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation

“…Many B-cell malignancies carry evidence of genomic instability affecting other loci (Bergsagel and Kuehl, 2001;Kuppers and Dalla-Favera, 2001;Fenton et al, 2002;Potter, 2003). A common target is the c-MYC gene, which encodes a key regulator of cell proliferation (Boxer and Dang, 2001).…”