Genomics: Global views of leukaemia
http://www.nature.com/nature/journal/v446/n7137/full/446739a.html
Genomic characterization of a type of leukaemia has resulted in the identification of common genetic abnormalities that underlie the disease. The results constitute an advance on several fronts.
Cancer is a genetic disease, caused largely by the acquisition of mutations in somatic cells after birth, or in some cases during developement. A search for these mutations was previously impossible, but progress in genomics technology holds the promise of making the complete characterization of the 'cancer genome' feasible. An important advance has been the development of high-density DNA microarrays for detecting regions of genomic amplification or deletion. The application of these arrays might allow for both a global view of recurring abnormalities in genomic copy number, and a sufficiently precise mapping of those abnormalities to allow the gene(s) affected to be identified. Recently, frequent deletions and loss-of-function mutations in the PAX5 gene in childhood acute lymphoblastic leukaemia were discovered. This disease results from a defect in the differentiation of blood cells: an overproduction of immature B lymphocytes that overtakes the normal development of blood cells in the bone marrow.
Most cases with a PAX5 deletion lacked mutations in the remaining copy (allele) of the PAX5 gene. This is strong evidence for 'haploinsufficiency', the situation in which the single functional allele cannot produce enough of the protein product. PAX5 point mutations were also discovered, with all but one of the mutations occurred in only one of the two alleles, which also supports the idea of haploinsufficiency.
Another interesting finding was the frequent co-occurrence of PAX5 loss of function with particular molecular abnormalities, such as a chromosomal translocation resulting in the fusion of two genes. This is detectable at the time of birth in blood taken from the umbilical cord of infants who go on to develop this disease later, suggesting that additional genetic hits are required to produce the consequences of ETV6/RUNX1 fusion. So it seems that PAX5 haploinsufficiency may represent a collaborating event in the development of ETV6/RUNX1 leukaemias.
By discoverying these underlying genetic causes, better treatment therapies can be developed.
Genomic characterization of a type of leukaemia has resulted in the identification of common genetic abnormalities that underlie the disease. The results constitute an advance on several fronts.
Cancer is a genetic disease, caused largely by the acquisition of mutations in somatic cells after birth, or in some cases during developement. A search for these mutations was previously impossible, but progress in genomics technology holds the promise of making the complete characterization of the 'cancer genome' feasible. An important advance has been the development of high-density DNA microarrays for detecting regions of genomic amplification or deletion. The application of these arrays might allow for both a global view of recurring abnormalities in genomic copy number, and a sufficiently precise mapping of those abnormalities to allow the gene(s) affected to be identified. Recently, frequent deletions and loss-of-function mutations in the PAX5 gene in childhood acute lymphoblastic leukaemia were discovered. This disease results from a defect in the differentiation of blood cells: an overproduction of immature B lymphocytes that overtakes the normal development of blood cells in the bone marrow.
Most cases with a PAX5 deletion lacked mutations in the remaining copy (allele) of the PAX5 gene. This is strong evidence for 'haploinsufficiency', the situation in which the single functional allele cannot produce enough of the protein product. PAX5 point mutations were also discovered, with all but one of the mutations occurred in only one of the two alleles, which also supports the idea of haploinsufficiency.
Another interesting finding was the frequent co-occurrence of PAX5 loss of function with particular molecular abnormalities, such as a chromosomal translocation resulting in the fusion of two genes. This is detectable at the time of birth in blood taken from the umbilical cord of infants who go on to develop this disease later, suggesting that additional genetic hits are required to produce the consequences of ETV6/RUNX1 fusion. So it seems that PAX5 haploinsufficiency may represent a collaborating event in the development of ETV6/RUNX1 leukaemias.
By discoverying these underlying genetic causes, better treatment therapies can be developed.
posted by JulieAnnJohnson at 6:17 PM
0 Comments:
Post a Comment
<< Home