Rearrangements of Chromosome Band 1p36 in Non-Hodgkin’s Lymphoma

• Published in: Clinical cancer research 1999-06, Vol.5 (6), p.1401-1409
• Main Authors: DAVE, B. J, HESS, M. M, PICKERING, D. L, ZALESKI, D. H, PFEIFER, A. L, WEISENBURGER, D. D, ARMITAGE, J. O, SANGER, W. G
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Chromosome Breakage; Chromosomes, Human, Pair 1 - genetics; Female; Hematologic and hematopoietic diseases; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - genetics; Male; Medical sciences; Middle Aged; Translocation, Genetic - genetics
• ISSN: 1078-0432; 1557-3265

We studied 850 consecutive cases of histologically ascertained pretreatment non-Hodgkin’s lymphoma with cytogenetically abnormal clones. The diagnostic karyotypes revealed that 12% of these cases exhibited structural rearrangements involving chromosome band 1p36. Here, we describe the karyotypes of 53 cases containing a 1p36 rearrangement [often involving translocations of unknown material and presented as add(1)(p36)]. We used fluorescence in situ hybridization to determine the origin of the translocation partners. We report three different recurrent translocations involving 1p36. These include der(1)t(1;1)(p36;q21) (three cases), der(1)t(1;1)(p36;q25) (three cases), and der(1)t(1;9)(p36;q13) (four cases). Using cytogenetic and fluorescence in situ hybridization analyses, we have resolved the translocation partners in 31 cases. Rearrangements of band 1p36 were found among different histopathological subtypes. Alterations of 1p36 never occurred as a sole abnormality, and in 42 of 53 cases, alterations of the band 14q32 were observed. The t(14;18)(q32;q21) translocation was present in 35 cases. The significantly high occurrence of 1p36 breakpoint in structural rearrangements and its involvement in recurrent translocations suggest that the region is bearing gene(s) that are important in lymphomagenesis. Our study also showed that cytogenetically evident deletions were frequent in chromosome 1p, almost always involving the p36 region, whereas duplications were rare and never encompassed the p36 region. Chromosome band 1p36 harbors many candidate tumor suppressor genes, and we propose that one or more of these genes might be deleted or functionally disrupted as a molecular consequence of the rearrangements, thus contributing to lymphomagenesis.