Dic(17;18)(p11.2;p11.2) is a recurring abnormality in chronic lymphocytic leukaemia associated with aggressive disease.
Interphase cytogenetics are commonly used to identify clonal abnormalities in chronic lymphocytic leukemia (CLL) patients but fail to identify recurrent translocations that ultimately can direct more focused molecular characterization. Given the importance of del(17p13.1) in CLL outcome, we performed an extensive review of 1213 patients undergoing metaphase cytogenetics at our institution and identified 16 (1.3%) with a recurrent unbalanced translocation between the p arms of chromosomes 17 and 18 that results in a dicentric chromosome with loss of much of 17p and 18p. The dic(17;18)(p11.2;p11.2) was associated with a complex (three or more unrelated cytogenetic abnormalities) karyotype in 12 patients (75%) at the time that the abnormality was first identified, and eventually associated with a complex karyotype in 94% of patients. IGHV mutational analysis was un-mutated in 88% of cases where evaluation was possible. Except for one patient who was diagnosed with CLL incidentally during a workup for metastatic tonsillar cancer, all patients identified with dic(17;18)(p11.2;p11.2) met criteria for disease treatment, with a median time from diagnosis to first treatment of 15 months. Our data demonstrate that dic(17;18)(p11.2;p11.2) is a novel recurrent cytogenetic abnormality in CLL associated with early age at diagnosis and accelerated disease progression. Future efforts to identify genes disrupted by this translocation are warranted and ongoing.
Woyach
Jennifer A
JA
The Ohio State University, Columbus, USA.
Heerema
Nyla A
NA
Zhao
John
J
McFaddin
Andrew
A
Stark
Amy
A
Lin
Thomas S
TS
Andritsos
Leslie A
LA
Blum
Kristie A
KA
Flynn
Joseph M
JM
Jones
Jeffrey A
JA
Byrd
John C
JC
D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D020732:Cytogenetic Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D014178:Translocation, Genetic