Analysis of balanced rearrangements of chromosome 6 in acute leukemia: clustered breakpoints in q22-q23 and possible involvement of c-MYB in a new recurrent translocation, t(6;7)(q23;q32 through 36).
OBJECTIVE
Many clinically important oncogenes and tumor suppressor genes have been identified through analysis of recurrent chromosomal rearrangements in acute leukemia. The contribution of sporadic rearrangements to malignancy is less clear and few have been mapped in detail. In this study we investigated the significance of novel translocations and inversions of 6q in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).


METHODS
Breakpoints of balanced 6q rearrangements were mapped in sequential fluorescent in situ hybridization (FISH) experiments with BAC and PAC clones in 11 patients.


RESULTS
Six of seven breakpoints in ALL and two in a single case of AML were localized to within a 10.5 Mb hotspot at 6q22-q23 with five analyzed to the level of a single probe. In two cases of childhood T-ALL, both carrying a t(6;7)(q23;q32 through 36), split FISH signals were produced by adjacent PAC, mapping the breakpoints to within an approximately 150 Kb region containing the genes c-MYB and AHI1. Five similar rearrangements, four also in pediatric T ALL were identified in the literature. Other 6q22-q23 translocations mapped in detail interrupted regions containing no recognized genes. 6q breakpoints outside the q22-q23 region were widely dispersed and in two were mapped to positions overlapping the cloned fragile sites FRA6E and FRA6F. The involvement of MLL was demonstrated in one case with t(6;11)(q15;q23).


CONCLUSIONS
We identified a new primary recurrent translocation t(6;7) (q22;q23 through q26) in pediatric T-ALL. Other translocations interrupting the 6q22-q23 breakpoint cluster region did not appear to be recurrent and may contribute to leukemogenesis through a novel mechanism. Key words; chromosome 6, translocation, c-Myb, AHI1.
Sinclair
Paul
P
Haematology Department, Royal Free and University College School of Medicine, Rowland Hill Street, London NW3 2PF, UK.
Harrison
Christine J
CJ
Jarosová
Marie
M
Foroni
Letizia
L
D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport; D000293:Adolescent; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D019457:Chromosome Breakage; D007446:Chromosome Inversion / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics* / Q000648:ultrastructure; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics* / Q000648:ultrastructure; D002999:Clone Cells / Q000473:pathology; D005260:Female; D020570:Genes, myb; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic / Q000235:genetics*
C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D015514:Oncogene Proteins, Fusion