Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.
Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to provide molecular characterization of this histological and clinical transformation, comparative genomic hybridization was applied to 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25-26 (28%), +1q31-32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25-26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16-21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16-21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13-21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquisition of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.
Berglund
Mattias
M
Department of Molecular Medicine and Surgery, Karolinska University Hospital - Solna, Stockholm, Sweden. Mattias.Berglund@genpat.uu.se
Enblad
Gunilla
G
Thunberg
Ulf
U
Amini
Rose-Marie
RM
Sundström
Christer
C
Roos
Göran
G
Erlanson
Martin
M
Rosenquist
Richard
R
Larsson
Catharina
C
Lagercrantz
Svetlana
S
D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008224:Lymphoma, Follicular / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2