TY - JOUR
T1 - Location and function of critical genes in leukemogenesis inferred from cytogenetic abnormalities in hematologic malignancies
AU - Bernard, Olivier A.
N1 - Funding Information:
YTOGENETICS HAS LONG BEEN consid- C ered by many biologists involved in cancer researchf ar too imprecise an approach to deserve scientific consideration. Changes in this view occurred, first from the finding of nonrandomnesso f chromosomal abnormalities in malignant cells, and later from correlations between chromosome and gener earrangementsT. he relationshipsb etween gene and chromosomea bnormalitiesw ere not obvious in the early 1980sb ecauseth e resolution provided by the banding techniques used in cytogenetics was much less precise than could be achieved by molecular biology. An averagec hromosomeb and (-330 bands per neutral genome, or 22 autosomes +X, Paris Conference 1971) contains approximatively lo7 base pairs-a potentially very large number of genes. Recurrence of some chromosome abnormalities as From INSERiVl U434 and CNRS SD 401 No. 434, Institut de Ghahique A4okc&ire, Paris, France. Supported in part by Ligue Nation&e Contre le Canceu,L igue Nationale Contre le Cancer (Corn& de Paris), and Associution de Rechrche Contre le Cancer (ARC). Address reprint requestst o Roland Berger, MD, Dr SC, U434, Institut de GPnbtique Molt&hire, 27 rue Juliette Dodu, 7’010 Paris, France. CoBtight 0 2000 by WB. Saw&s Company 0037-19G3/00/3704-0009$10.00/0 hi:1 0.1053/shm.2000.16449 well as improvement in molecular techniquesl ed to the identification of specific genes involved in the chromosome rearrangementso f malignancies.T he study of Burkitt’s lymphoma-leukemia translocations had a stimulating effect on the evolution of attitudes toward this problem. The breakpoints of three recurrent translocationsf ound in theset umors were shown to be localizedw ithin the MyClocus on chromosome 8 and the immunoglobulin gene loci on chromosomes1 4, 2, and 22. These results acceleratedt he identification of other genes involved in chromo-somalr earrangements. More recently, the use of fluorescence in situ hybridization (FISH) asa complement to cytogenetic methods has provided a new tool to facilitate gene identification and allowed the discovery of new chromosomal rearrangements.A large number of genesi nvolved in normal hematopoieisish ave now been identified from molecular cytogenetic studieso f structural chromosomal rearrangementsi n various hematopoietic malignancies.
PY - 2000/1/1
Y1 - 2000/1/1
N2 - Dramatic advances in the cytogenetic analysis of chromosomal rearrangements of hematopoietic malignancies have occurred over the past years. These are due to considerable improvement in the techniques of molecular cytogenetics. Various applications of fluorescence in situ hybridization (FISH), used in conjunction with conventional cytogenetics, mare the recognition of some abnormalities easier, and the localization of chromosomal breakpoints in structural rearrangements more precise. Under many circumstances, accurate breakpoint localization is the first step toward the identification of genes involved in translocations and inversions. Some of the genes recently discovered may be rearranged with several partner genes. These promiscuous genes are natural experiments that generate mutants which help to identify the function of genes rearranged in hematopoietic malignancies as well as that of their normal counterparts. The diversity of the genes implicated in leukemogenesis mares their functional study a challenge, but, as recently shown by their role in chromatin remodeling, increasing recognition of cross-talk between many of these genes justifies the development of analyses of leukemia-associated chromosome abnormalities and of their functional consequences. (C) 2000 by W.B. Saunders Company.
AB - Dramatic advances in the cytogenetic analysis of chromosomal rearrangements of hematopoietic malignancies have occurred over the past years. These are due to considerable improvement in the techniques of molecular cytogenetics. Various applications of fluorescence in situ hybridization (FISH), used in conjunction with conventional cytogenetics, mare the recognition of some abnormalities easier, and the localization of chromosomal breakpoints in structural rearrangements more precise. Under many circumstances, accurate breakpoint localization is the first step toward the identification of genes involved in translocations and inversions. Some of the genes recently discovered may be rearranged with several partner genes. These promiscuous genes are natural experiments that generate mutants which help to identify the function of genes rearranged in hematopoietic malignancies as well as that of their normal counterparts. The diversity of the genes implicated in leukemogenesis mares their functional study a challenge, but, as recently shown by their role in chromatin remodeling, increasing recognition of cross-talk between many of these genes justifies the development of analyses of leukemia-associated chromosome abnormalities and of their functional consequences. (C) 2000 by W.B. Saunders Company.
UR - http://www.scopus.com/inward/record.url?scp=0033788685&partnerID=8YFLogxK
U2 - 10.1016/S0037-1963(00)90020-9
DO - 10.1016/S0037-1963(00)90020-9
M3 - Article
C2 - 11071362
AN - SCOPUS:0033788685
SN - 0037-1963
VL - 37
SP - 412
EP - 419
JO - Seminars in Hematology
JF - Seminars in Hematology
IS - 4
ER -