دورية أكاديمية
Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group.
| العنوان: | Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. |
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| المؤلفون: | Zhang, Jinghui, Mullighan, Charles G, Harvey, Richard C, Wu, Gang, Chen, Xiang, Edmonson, Michael, Buetow, Kenneth H, Carroll, William L, Chen, I-Ming, Devidas, Meenakshi, Gerhard, Daniela S, Loh, Mignon L, Reaman, Gregory H, Relling, Mary V, Camitta, Bruce M, Bowman, W Paul, Smith, Malcolm A, Willman, Cheryl L, Downing, James R, Hunger, Stephen P |
| المصدر: | Blood ; ISSN:1528-0020 ; Volume:118 ; Issue:11 |
| بيانات النشر: | Silverchair Information Systems |
| سنة النشر: | 2011 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | We sequenced 120 candidate genes in 187 high-risk childhood B-precursor acute lymphoblastic leukemias, the largest pediatric cancer genome sequencing effort reported to date. Integrated analysis of 179 validated somatic sequence mutations with genome-wide copy number alterations and gene expression profiles revealed a high frequency of recurrent somatic alterations in key signaling pathways, including B-cell development/differentiation (68% of cases), the TP53/RB tumor suppressor pathway (54%), Ras signaling (50%), and Janus kinases (11%). Recurrent mutations were also found in ETV6 (6 cases), TBL1XR1 (3), CREBBP (3), MUC4 (2), ASMTL (2), and ADARB2 (2). The frequency of mutations within the 4 major pathways varied markedly across genetic subtypes. Among 23 leukemias expressing a BCR-ABL1-like gene expression profile, 96% had somatic alterations in B-cell development/differentiation, 57% in JAK, and 52% in both pathways, whereas only 9% had Ras pathway mutations. In contrast, 21 cases defined by a distinct gene expression profile coupled with focal ERG deletion rarely had B-cell development/differentiation or JAK kinase alterations but had a high frequency (62%) of Ras signaling pathway mutations. These data extend the range of genes that are recurrently mutated in high-risk childhood B-precursor acute lymphoblastic leukemia and highlight important new therapeutic targets for selected patient subsets. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1182/blood-2011-03-341412Test; https://pubmed.ncbi.nlm.nih.gov/21680795Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175785Test/ |
| DOI: | 10.1182/blood-2011-03-341412 |
| الإتاحة: | https://doi.org/10.1182/blood-2011-03-341412Test https://pubmed.ncbi.nlm.nih.gov/21680795Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175785Test/ |
| رقم الانضمام: | edsbas.E78D9052 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1182/blood-2011-03-341412 |
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