Recurrent Chromosomal Rearrangements and a Homozygous Deletion Spanning 1-Mb Region at 10p11.2 in Adult T-Cell Leukemia/Lymphoma.

Cytogenetic analyses and their correlation with clinical features are still limited in mature T-cell malignancies. The cytogenetics of adult T-cell leukemia/lymphoma (ATLL) is complicated by many structural and numerical abnormalities of chromosomes. Thus, it is occasionally difficult to define karyotype of ATLL only by chromosomal banding method. Using multicolor spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH), we performed molecular-cytogenetic studies on 38 patients with adult T-cell leukemia/lymphoma (ATLL) and 7 established cell lines. In SKY analysis, chromosomal bands involved in rearrangements were identified based on the inverted images of DAPI staining. Chromosome no.7 (25 cases) and no.14 (30) were frequently involved in structural rearrangements including translocations, inversions, insertions, isochromosomes, and deletions. Breakages frequently occurred at 10p11-13 (21 cases, 46.6%), and 14q11.2 (16, 35.6%), 14q32 (12, 26.7%), 7q22 (10, 22.2%), 9q22 (10, 22.2%), 13q14 (9, 20.0%), 22p11 (8, 17.7%), 8p11 (7, 15.5%), 18p11 (7, 15.5%), 21q22 (7, 15.5%) and 19q13 (6, 13.3%). Recurrent partners associated with 10p11.2-13 rearrangements were 21q22 (3 cases), 13q14 (2) and 14q32.1 (2). Partner chromosomal breakpoints involving 14q11.2 rearrangements were 14q32 (3 cases), 8p11.2-21 (3), and 11q13.3 (2), while those involved in 14q32 rearrangements were 14q11 (3) and 10p11-13 (2). Using FISH with 37 bacterial artificial chromosome clones, we analyzed breakpoints at 10p11.2-13 in two cell lines KOB4 and KK1 and one patient (HH) by walking a segment ranging from 10p13 to 10p11.2. Among 37 BAC clones used as FISH probes, 9 were assigned to 10p15, 3 to 10p14-13, and the remaining 25 to 10p11.2-12. Large genomic deletions were detected at 10p11.2 on der(10) in two cell lines. In patient HH, a homozygous deletion was identified at 10p11.2, spanning the region of 1 Mb in size. Chromosome 14q32 translocation was associated with shorter survival (median survival time; 4.2 months vs. 8.0 months), although statistically not significant. As for 10p11.2-13 and 14q11.2 rearrangements, there was no significant difference of survival between patients with and without respective abnormalities. In conclusion, SKY and FISH analysis identified recurrent chromosomal rearrangements and a homozygous deletion at 10p11.2 in ATLL. Our molecular analysis is now focusing on this genomic region to clone genes associated with development of ATLL.