Academic Bibliography

 Search 200 years of publications by Ghent University researchers.
Advanced search
1 file | 1.73 MB
Add to list
  1. Search results
  2. Integrative genomic analysis implicat...

Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia

Jennifer R Brown, Megan Hanna, Bethany Tesar, Lilian Werner, Nathalie Pochet (UGent) , John M Asara, Yaoyu E Wang, Paola dal Cin, Stacey M Fernandes, Christina Thompson, et al.
(2012) CLINICAL CANCER RESEARCH. 18(14). p.3791-3802
Author
Organization
Project
Abstract
Purpose: The disease course of chronic lymphocytic leukemia (CLL) varies significantly within cytogenetic groups. We hypothesized that high-resolution genomic analysis of CLL would identify additional recurrent abnormalities associated with short time-to-first therapy (TTFT). Experimental Design: We undertook high-resolution genomic analysis of 161 prospectively enrolled CLLs using Affymetrix 6.0 SNP arrays, and integrated analysis of this data set with gene expression profiles. Results: Copy number analysis (CNA) of nonprogressive CLL reveals a stable genotype, with a median of only 1 somatic CNA per sample. Progressive CLL with 13q deletion was associated with additional somatic CNAs, and a greater number of CNAs was predictive of TTFT. We identified other recurrent CNAs associated with short TTFT: 8q24 amplification focused on the cancer susceptibility locus near MYC in 3.7%; 3q26 amplifications focused on PIK3CA in 5.6%; and 8p deletions in 5% of patients. Sequencing of MYC further identified somatic mutations in two CLLs. We determined which catalytic subunits of phosphoinositide 3-kinase (PI3K) were in active complex with the p85 regulatory subunit and showed enrichment for the a subunit in three CLLs carrying PIK3CA amplification. Conclusions: Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL.
Keywords
ABERRATIONS, SURVIVAL, 13Q14 DELETIONS, GENE, B-CELL, C-MYC, COLORECTAL-CANCER, EMBRYONIC STEM, RISK, ASSOCIATION

Downloads

  • Download
    (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 1.73 MB

Citation

Please use this url to cite or link to this publication:

MLA
Brown, Jennifer R., et al. “Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia.” CLINICAL CANCER RESEARCH, vol. 18, no. 14, 2012, pp. 3791–802, doi:10.1158/1078-0432.CCR-11-2342.
APA
Brown, J. R., Hanna, M., Tesar, B., Werner, L., Pochet, N., Asara, J. M., … Freedman, A. S. (2012). Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia. CLINICAL CANCER RESEARCH, 18(14), 3791–3802. https://doi.org/10.1158/1078-0432.CCR-11-2342
Chicago author-date
Brown, Jennifer R, Megan Hanna, Bethany Tesar, Lilian Werner, Nathalie Pochet, John M Asara, Yaoyu E Wang, et al. 2012. “Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia.” CLINICAL CANCER RESEARCH 18 (14): 3791–3802. https://doi.org/10.1158/1078-0432.CCR-11-2342.
Chicago author-date (all authors)
Brown, Jennifer R, Megan Hanna, Bethany Tesar, Lilian Werner, Nathalie Pochet, John M Asara, Yaoyu E Wang, Paola dal Cin, Stacey M Fernandes, Christina Thompson, Laura MacConaill, Catherine J Wu, Yves Van de Peer, Mick Correll, Aviv Regev, Donna Neuberg, and Arnold S Freedman. 2012. “Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia.” CLINICAL CANCER RESEARCH 18 (14): 3791–3802. doi:10.1158/1078-0432.CCR-11-2342.
Vancouver
1.
Brown JR, Hanna M, Tesar B, Werner L, Pochet N, Asara JM, et al. Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia. CLINICAL CANCER RESEARCH. 2012;18(14):3791–802.
IEEE
[1]
J. R. Brown et al., “Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia,” CLINICAL CANCER RESEARCH, vol. 18, no. 14, pp. 3791–3802, 2012.
@article{2997248,
  abstract     = {{Purpose: The disease course of chronic lymphocytic leukemia (CLL) varies significantly within cytogenetic groups. We hypothesized that high-resolution genomic analysis of CLL would identify additional recurrent abnormalities associated with short time-to-first therapy (TTFT).
Experimental Design: We undertook high-resolution genomic analysis of 161 prospectively enrolled CLLs using Affymetrix 6.0 SNP arrays, and integrated analysis of this data set with gene expression profiles.
Results: Copy number analysis (CNA) of nonprogressive CLL reveals a stable genotype, with a median of only 1 somatic CNA per sample. Progressive CLL with 13q deletion was associated with additional somatic CNAs, and a greater number of CNAs was predictive of TTFT. We identified other recurrent CNAs associated with short TTFT: 8q24 amplification focused on the cancer susceptibility locus near MYC in 3.7%; 3q26 amplifications focused on PIK3CA in 5.6%; and 8p deletions in 5% of patients. Sequencing of MYC further identified somatic mutations in two CLLs. We determined which catalytic subunits of phosphoinositide 3-kinase (PI3K) were in active complex with the p85 regulatory subunit and showed enrichment for the a subunit in three CLLs carrying PIK3CA amplification.
Conclusions: Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL.}},
  author       = {{Brown, Jennifer R and Hanna, Megan and Tesar, Bethany and Werner, Lilian and Pochet, Nathalie and Asara, John M and Wang, Yaoyu E and dal Cin, Paola and Fernandes, Stacey M and Thompson, Christina and MacConaill, Laura and Wu, Catherine J and Van de Peer, Yves and Correll, Mick and Regev, Aviv and Neuberg, Donna and Freedman, Arnold S}},
  issn         = {{1078-0432}},
  journal      = {{CLINICAL CANCER RESEARCH}},
  keywords     = {{ABERRATIONS,SURVIVAL,13Q14 DELETIONS,GENE,B-CELL,C-MYC,COLORECTAL-CANCER,EMBRYONIC STEM,RISK,ASSOCIATION}},
  language     = {{eng}},
  number       = {{14}},
  pages        = {{3791--3802}},
  title        = {{Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-11-2342}},
  volume       = {{18}},
  year         = {{2012}},
}
Altmetric
View in Altmetric
Web of Science
Times cited: