Genetic Abnormalities

Numerous molecular events have been associated with the process of transformation. Several groups have found mutations in the p53 tumor suppressor gene in transformed lymphomas.42 43 Occasionally, p53 mutations can be identified in patients with follicular lymphoma prior to transformation, and this finding in nontranformed follicular lymphoma may be associated with a poor prognosis.42 Mutations in the bcl-6 gene have also been associated with progression from follicular lymphoma to diffuse large B-cell lymphoma. The Stanford group identified bcl-6 translocations in 39% of follicular lymphomas that were known to have subsequently transformed, as compared with 14.1% in biopsies from patients that were not known to have transformed (P = 0.0048).44 Rearrangements of myc have also been identified in transformed lymphomas and the presence of these rearrangements in follicular lymphomas may be associated with a poor prognosis and greater risk of transformation.34 cDNA microarray analysis of transformed lymphomas has demonstrated patterns of increased expression of c-myc and associated targets in some specimens and decreased expression of these genes in others.45 In addition, expression

Table 67.2 Genetic abnormalities associated with transformation of follicular lymphoma

Genetic abnormality References p53 mutation 42, 43

Table 67.2 Genetic abnormalities associated with transformation of follicular lymphoma

Genetic abnormality References p53 mutation 42, 43

myc rearrangement/altered expression

34, 35, 45, 49

bcl-2 mutation/dysregulation

28, 50

bcl-6 mutation

32, 44

p15 and p16 loss/gene alteration

46, 47, 51

Cytogenetic abnormalities

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