Aberrant somatic hypermutations in thyroid lymphomas.
To determine a possible role of aberrant somatic hypermutation (ASHM) in the pathogenesis of thyroid lymphoma (TL), mutational status of genes affected by ASHM, including c-MYC, PIM-1, PAX-5 and RhoH/TTF, was analyzed. Tumor specimens from 33 patients with thyroid B-cell lymphoma and 14 with chronic lymphocytic thyroiditis (CLTH), an autoimmune thyroiditis known to provide a basis for TL development, was examined. Mutations of at least one of these genes was detected in 16 of 33 (48.5%) patients with TL and in 2 of 14 (14.3%) CLTH. Occurrence of ASHM in PIM-1, RhoH/TTF, and c-MYC was a constant finding in follicular lymphoma (FL) (all of 11 cases) but not so frequent in diffuse large B-cell lymphoma (DLBCL) (4 (33.3%) of 12 cases) and Marginal zone B-cell lymphoma (MZBCL) (1 (10.0%) of 10 cases). ASHM activity is ongoing in most of FL and DLBCL because intraclonal variants were found. FL was also unique in its lower expression level of activation-induced cytidine deaminase, a main player in DNA-modifying processes during SHM, compare to DLBCL and MZBCL.
Takakuwa
Tetsuya
T
Human Health Science, Kyoto University Graduate School of Medicine, 606-8507 Sakyo-ku, Shogoin Kawahara-cyo 53, Kyoto, Japan. tez@hs.med.kyoto-u.ac.jp
Miyauchi
Akira
A
Aozasa
Katsuyuki
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics*