A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia

Klein, Annelies de; Kessel, Ad Geurts van; Grosveld, Gerard; Bartram, Claus R.; Hagemeijer, Anne; Bootsma, D.; Spurr, Nigel K.; Heisterkamp, Nora; Groffen, John; Stephenson, John

doi:10.1038/300765a0

Cited by 1,274 publications

(477 citation statements)

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“…Traditionally, genome-wide discovery efforts were performed using FISH or array-based methods, leading to the identification of translocations, for example, those common to Chronic Myelogenous Leukemia (CML) and Burkitt’s lymphoma[98, 99]. These assays were limited to analyzing large translocations or copy number changes.…”

Section: Mps Applications In Mutation Analysismentioning

confidence: 99%

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Gundry

Vijg

2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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DNA mutations are the source of genetic variation within populations. The majority of mutations with observable effects are deleterious. In humans mutations in the germ line can cause genetic disease. In somatic cells multiple rounds of mutations and selection lead to cancer. The study of genetic variation has progressed rapidly since the completion of the draft sequence of the human genome. Recent advances in sequencing technology, most importantly the introduction of massively parallel sequencing (MPS), have resulted in more than a hundred-fold reduction in the time and cost required for sequencing nucleic acids. These improvements have greatly expanded the use of sequencing as a practical tool for mutation analysis. While in the past the high cost of sequencing limited mutation analysis to selectable markers or small forward mutation targets assumed to be representative for the genome overall, current platforms allow whole genome sequencing for less than $5,000. This has already given rise to direct estimates of germline mutation rates in multiple organisms including humans by comparing whole genome sequences between parents and offspring. Here we present a brief history of the field of mutation research, with a focus on classical tools for the measurement of mutation rates. We then review MPS, how it is currently applied and the new insight into human and animal mutation frequencies and spectra that has been obtained from whole genome sequencing. While great progress has been made, we note that the single most important limitation of current MPS approaches for mutation analysis is the inability to address low-abundance mutations that turn somatic tissues into mosaics of cells. Such mutations are at the basis of intra-tumor heterogeneity, with important implications for clinical diagnosis, and could also contribute to somatic diseases other than cancer, including aging. Some possible approaches to gain access to low-abundance mutations are discussed, with a brief overview of new sequencing platforms that are currently waiting in the wings to advance this exploding field even further.

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Section: Mps Applications In Mutation Analysismentioning

confidence: 99%

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Gundry

Vijg

2012

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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“…Molecular analyses delineated the amplicon as a 500-kb region from chromosome band 9q34, containing the oncogenes ABL1 and NUP214 (refs. 5,6). We identified a previously undescribed mechanism for activation of tyrosine kinases in cancer: the formation of episomes resulting in a fusion between NUP214 and ABL1.…”

mentioning

confidence: 99%

“…The Philadelphia translocation, resulting in the BCR-ABL1 fusion gene, is typically found in chronic myeloid leukemia (CML) and precursor B-cell acute lymphoblastic leukemia (B-ALL) but is exceptionally rare in T-ALL 2,5,10 . To study the potential involvement of ABL1 rearrangements in T-ALL, we screened 90 cases by fluorescence in situ hybridization (FISH), using BCR and ABL1 probes.…”

mentioning

confidence: 99%

Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia

et al. 2004

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“…Chronic myelogenous leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) are clonal proliferative disorders associated with the t(9;22) translocation whereby the breakpoint cluster region (bcr) on chromosome 22 juxtaposes to the c-Abl gene on chromosome 9. The chimeric gene generates a fusion protein containing the ®rst 927 or 902 aminoacids (aa) of Bcr in CML, while in ALL only the ®rst 426 aa of Bcr are fused to c-Abl (Chan et al, 1987;de Klein et al, 1982;Kurzrock et al, 1987). Both Bcr-Abl fusion proteins exhibit an increased tyrosine kinase activity and their oncogenic potential has been demonstrated using in vitro cell culture systems as well as in in vivo mouse models (Daley and Baltimore, 1988;Gishizky and White, 1992;Lugo et al, 1990;Lugo and Witte, 1989;McLaughlin et al, 1987;Young and Witte, 1988).…”

Section: Introductionmentioning

confidence: 99%

The SH2-containing adapter protein GRB10 interacts with BCR-ABL

et al. 1998

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A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia

Cited by 1,274 publications

References 26 publications

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Direct mutation analysis by high-throughput sequencing: From germline to low-abundant, somatic variants

Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia

The SH2-containing adapter protein GRB10 interacts with BCR-ABL

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