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somatic hypermutation

Monday 7 November 2005

Normal GC B cells undergo immunoglobulin gene editing via somatic hypermutation (SHM) of their rearranged IgV region genes.

This process specifically targets regulatory sequences downstream of the IgV gene promoter.

DLBCLs typically have evidence of SHM, indicating that these tumors likely originate from GC or post-GC B cells.

The 5’ regulatory regions of other GC genes, BCL6 and CD95 (FAS), are also known targets of physiologic SHM.

Pathology (aberrant SHM)

SHM may also occur aberrantly and is postulated to be an additional pathogenetic mechanism in DLBCL.

Genes aberrantly targeted by SHM include BCL6, PIM1, cMYC, PAX5, and RhoH/TTF. Like BCL6, FAS(CD95) has been postulated to be targeted by both physiologic and aberrant SHM.

Because the SHM machinery targets broad regions of multiple genes, the specific consequences of aberrant SHM may be quite different in individual tumors.

References

- Abramson JS, Shipp MA. Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach. Blood. 2005 Aug 15;106(4):1164-74. Epub 2005 Apr 26. PMID: 15855278