Difference between revisions of "BCR"
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The function of the normal BCR gene product is as a GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. The protein has serine/threonine kinase activity. (1) | The function of the normal BCR gene product is as a GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. The protein has serine/threonine kinase activity. (1) | ||
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| + | By far the most prevalent BCR alteration associated with cancer are the fusions of the BCR gene with the ABL1 gene. A reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus) produces the Philadelphia chromosome t(9;22)(q34.1;q11.2), which is prevalent in Chronic Myeloid Leukemia (1, 2) and to a lesser extent in B-cell Acute Lymphoblastic Leukemia and T-cell Acute Lymphoblastic Leukemia. The head to tail arrangement of the BCR-ABL1 fusion gene results in an activated tyrosine kinase activity (6). | ||
Mention that is haas coiled coil domain and prob. aggregates as Fusion BRC-ABL1. | Mention that is haas coiled coil domain and prob. aggregates as Fusion BRC-ABL1. | ||
Revision as of 12:07, 22 June 2018
Primary Author(s)*
Brian Davis, PhD
Synonyms
BCR, RhoGEF and GTPase activating protein; Breakpoint Cluster Region; BCR1; ALL; CML; PHL; D22S11; D22S662
Genomic Location
Cytoband: 22q11.23
Genomic Coordinates:
GRCh38.p12 23180365..23318037
Cancer Category/Type
Chronic Myeloid Leukemia (also referred as (Chronic Myelogenous Leukemia)
More than 90% of patients diagnosed with Chronic Myeloid Leukemia bear a Philadelphia chromosome t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus (1, also see OMIM). The Drug Imatinib mesylate, also known as Gleevec, was the one of the first molecularly developed drugs, and has a remarkably high success rate in treatment of patients with Chronic Myeloid Leukemia (5)
Approximately 20% of patients (25 - 30% of adult and 2 - 10% of children) diagnosed with Acute Lymphoblastic Leukemia bear a Philadelphia chromosome t(9;22)(q34.1;q11.2), which is a reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus) (1, also see OMIM). Treatment of Acute Lymphoblastic Leukemia patients with Gleevec do not have the same success as Chronic Myeloid Leukemia patients treated with Gleevec, as the genomic instability of ALL cells contribute to point mutations arising in the BRC-ABL kinase domain, leading to resistance to Gleevec (4).
Gene Overview
The function of the normal BCR gene product is as a GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. The protein has serine/threonine kinase activity. (1)
By far the most prevalent BCR alteration associated with cancer are the fusions of the BCR gene with the ABL1 gene. A reciprocal translocation between chromosome 22 (BCR locus) and chromosome 9 (ABL1 locus) produces the Philadelphia chromosome t(9;22)(q34.1;q11.2), which is prevalent in Chronic Myeloid Leukemia (1, 2) and to a lesser extent in B-cell Acute Lymphoblastic Leukemia and T-cell Acute Lymphoblastic Leukemia. The head to tail arrangement of the BCR-ABL1 fusion gene results in an activated tyrosine kinase activity (6).
Mention that is haas coiled coil domain and prob. aggregates as Fusion BRC-ABL1.
Common Alteration Types
BCR-ABL1
BCR-JAK2
BCR-FGFR1
BCR-PDCFRA
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X | EXAMPLE: X |
Internal Pages
Put your text here
EXAMPLE Germline Cancer Predisposition Genes
External Links
Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.
EXAMPLES
BCR by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
BCR by COSMIC - sequence information, expression, catalogue of mutations
BCR-ABL1 by CIViC - general knowledge and evidence-based variant specific information
BCR by St. Jude ProteinPaint mutational landscape and matched expression data.
BCR by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
BCR by Cancer Index - gene, pathway, publication information matched to cancer type
BCR-ABL1 by OncoKB - mutational landscape, mutation effect, variant classification
BCR by My Cancer Genome - brief gene overview
BCR by UniProt - protein and molecular structure and function
BCR by Pfam - gene and protein structure and function information
BCR by GeneCards - general gene information and summaries
BCR by OMIM - compendium of human genes and genetic phenotypes
References
1. Diekmann D. et al. (1991). Bcr encodes a GTPase-activating protein for p21rac. Nature 35: 400-2. PMID 1903516 DOI: 10.1038/351400a0
Notes
*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.