High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients

Daniel R. Carrasco; Giovanni Tonon; Yongsheng Huang; Yunyu Zhang; Raktim Sinha; Bin Feng; James P. Stewart; Fenghuang Zhan; Deepak Khatry; Marina Protopopova; Alexei Protopopov; Kumar Sukhdeo; Ichiro Hanamura; Owen Stephens; Bart Barlogie; Kenneth C. Anderson; Lynda Chin; John D. Shaughnessy; Cameron Brennan; Ronald A. DePinho

doi:10.1016/j.ccr.2006.03.019

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients

Daniel R. Carrasco, Giovanni Tonon, Yongsheng Huang, Yunyu Zhang, Raktim Sinha, Bin Feng, James P. Stewart, Fenghuang Zhan, Deepak Khatry, Marina Protopopova, Alexei Protopopov, Kumar Sukhdeo, Ichiro Hanamura, Owen Stephens, Bart Barlogie, Kenneth C. Anderson, Lynda Chin, John D. Shaughnessy, Cameron Brennan, Ronald A. DePinho

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article › peer-review

Abstract

To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.

Original language	English
Pages (from-to)	313-325
Number of pages	13
Journal	Cancer Cell
Volume	9
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2006.03.019
Publication status	Published - Apr 2006

Keywords

CELLCYCLE

ASJC Scopus subject areas

Cancer Research
Cell Biology
Oncology

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Carrasco, D. R., Tonon, G., Huang, Y., Zhang, Y., Sinha, R., Feng, B., Stewart, J. P., Zhan, F., Khatry, D., Protopopova, M., Protopopov, A., Sukhdeo, K., Hanamura, I., Stephens, O., Barlogie, B., Anderson, K. C., Chin, L., Shaughnessy, J. D., Brennan, C., & DePinho, R. A. (2006). High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell, 9(4), 313-325. https://doi.org/10.1016/j.ccr.2006.03.019

High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. / Carrasco, Daniel R.; Tonon, Giovanni; Huang, Yongsheng; Zhang, Yunyu; Sinha, Raktim; Feng, Bin; Stewart, James P.; Zhan, Fenghuang; Khatry, Deepak; Protopopova, Marina; Protopopov, Alexei; Sukhdeo, Kumar; Hanamura, Ichiro; Stephens, Owen; Barlogie, Bart; Anderson, Kenneth C.; Chin, Lynda; Shaughnessy, John D.; Brennan, Cameron; DePinho, Ronald A.

In: Cancer Cell, Vol. 9, No. 4, 04.2006, p. 313-325.

Research output: Contribution to journal › Article › peer-review

Carrasco, DR, Tonon, G, Huang, Y, Zhang, Y, Sinha, R, Feng, B, Stewart, JP, Zhan, F, Khatry, D, Protopopova, M, Protopopov, A, Sukhdeo, K, Hanamura, I, Stephens, O, Barlogie, B, Anderson, KC, Chin, L, Shaughnessy, JD, Brennan, C & DePinho, RA 2006, 'High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients', Cancer Cell, vol. 9, no. 4, pp. 313-325. https://doi.org/10.1016/j.ccr.2006.03.019

Carrasco, Daniel R. ; Tonon, Giovanni ; Huang, Yongsheng ; Zhang, Yunyu ; Sinha, Raktim ; Feng, Bin ; Stewart, James P. ; Zhan, Fenghuang ; Khatry, Deepak ; Protopopova, Marina ; Protopopov, Alexei ; Sukhdeo, Kumar ; Hanamura, Ichiro ; Stephens, Owen ; Barlogie, Bart ; Anderson, Kenneth C. ; Chin, Lynda ; Shaughnessy, John D. ; Brennan, Cameron ; DePinho, Ronald A. / High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. In: Cancer Cell. 2006 ; Vol. 9, No. 4. pp. 313-325.

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abstract = "To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using nonnegative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients.",

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AU - Stephens, Owen

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