Rameen Beroukhim, MD, PhD
Office phone: 617-632-2166
Preferred contact method: appointment phone
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Glioma, Meningioma, Somatic genetics of cancer
Area of Research
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
- V Scholar Award, 2009
Our research team focuses on understanding the genetic changes in cancer and how these genetic changes affect cancer behavior. We have a particular focus on brain cancers, although we study many types of cancer. All our projects involve collaborations with multiple other groups at the DFCI, Broad Institute, and multiple other institutions.
We have undertaken a variety of genomic approaches to profiling large numbers of cancers, including the use of SNP arrays, expression arrays, and sequencing. We have also developed several computational approaches to understand these data.
For copy-number changes, which are some of the most frequent somatic genetic events in cancer, we developed an approach (GISTIC, for Genomic Identification of Significant Targets In Cancer) that simultaneously identifies those events that are most likely to drive cancer development and profiles individual specimens for the set of events they have undergone. We have used this approach to identify new oncogenes in several cancer types, including lung, esophageal, and colorectal cancers. We published an analysis of over 3000 cancer copy-number profiles in 2010, which is one of the most-cited publications in cancer from that year. This study identified two new amplified oncogenes (MCL1 and BCL2L1) and showed both lineage-specific genetic events and events that were shared across many cancer types. We have also used this approach to identify prognostic indicators in endometrial cancers and predictors of pathway dependency several cancer types, including glioblastoma and renal cancer.
We have performed integrated genomic analyses across multiple datasets. For example, we have integrated copy-number data with functional screens to identify novel vulnerabilities associated with genomic losses in cancer.
We have performed high-throughput sequencing analyses of several cancer types. For example, we found mutations in SMO and AKT1 in meningiomas, which may serve as therapeutic targets in these diseases. We have also found rearrangements of MYBL1 in pediatric low-grade gliomas.
- Beroukhim R1, Getz G1, Nghiemphu L, Barretina J, Hsueh T, Linhart D, Vivanco I, Lee JC, Huang JH, Alexander S, Du J, Kau T, Thomas RK, Shah K, Soto H, Perner S, Prensner J, Debiasi RM, Demichelis F, Hatton C, Rubin MA, Garraway LA, Nelson SF, Liau L, Mischel PS, Cloughesy TF, Meyerson M, Golub TA, Lander ES, Mellinghoff IK, Sellers WR. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA. 2007;104:20007-12. PMC2148413.
- Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 2008; 455:1061-8.
- Beroukhim R, Brunet JP, Di Napoli A, Mertz KD, Seeley A, Pires MM, Linhart D, Worrell RA, Moch H, Rubin MA, Sellers WR, Meyerson M, Linehan WM, Kaelin WG Jr, Signoretti S. Patterns of gene expression and copy-number alterations in von-hippel landau disease associated and sporadic clear cell carcinoma in the kidney. Cancer Res., 2009; 69:4674-81
- Salvesen HB, Carter SL, Mannelqvist M, Dutt A, Getz G, Stefansson IM, Raeder MB, Sos ML, Engelsen IB, Trovik J, Wik E, Greulich H, B TH, Jonassen I, Thomas RK, Zander T, Garraway LA, Oyan AM, Sellers WR, Kalland KH, Meyerson M, Akslen LA, Beroukhim R. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci USA, 2009; 106:4834-9.
- Beroukhim R1, Mermel C1, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffmann C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, DeMichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature, 2010;463(7283):899-905. PMCID: PMC2826709
- Mermel CH, Schumacher SE, Hill B, Meyerson ML, Beroukhim R1, Getz G1. GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers. Genome Biol. 2011;12(4):R41. PMCID: PMC3218867
- Dulak AM, Schumacher SE, van Lieshout J, Imamura Y, Fox C, Shim B, Ramos AH, Saksena G, Baca SC, Baselga J, Tabernero J, Barretina J, Enzinger PC, Corso G, Roviello F, Lin L, Bandla S, Luketich JD, Pennathur A, Meyerson M, Ogino S, Shivdasani RA, Beer DG, Godfrey TE, Beroukhim R1, Bass AJ1. Gastrointestinal Adenocarcinomas of the Esophagus, Stomach, and Colon Exhibit Distinct Patterns of Genome Instability and Oncogenesis. Cancer Res. 2012 Sep 1;72(17):4383-4393.
- Nijhawan D, Zack TI, Ren Y, Strickland MR, Lamothe R, Schumacher SE, Tsherniak A, Besche HC, Rosenbluh J, Shehata S, Cowley GS, Weir BA, Goldberg AL, Mesirov JP, Root DE, Bhatia SN, Beroukhim R1, Hahn WC1. Cancer vulnerabilities unveiled by genomic loss. Cell. 2012 Aug 17;150(4):842-54.
- Brastianos PK, Horowitz PM, Santagata S, Jones RT, McKenna A, Getz G, Ligon KL, Palescandolo E, Van Hummelen P, Ducar MD, Raza A, Sunkavalli A, Macconaill LE, Stemmer-Rachamimov AO, Louis DN, Hahn WC1, Dunn IF1, Beroukhim R1. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013 Jan 20; 45(3):285-9.
- Ramkissoon LA, Horowitz PM, Craig JM, Ramkissoon SH, Rich BE, Schumacher SE, McKenna A, Lawrence MS, Bergthold G, Brastianos PK, Tabak B, Ducar MD, Van Hummelen P, Macconaill LE, Pouissant-Young T, Cho YJ, Taha H, Mahmoud M, Bowers DC, Margraf L, Tabori U, Hawkins C, Packer RJ, Hill DA, Pomeroy SL, Eberhart CG, Dunn IF, Goumnerova L, Getz G, Chan JA, Santagata S, Hahn WC, Stiles CD, Ligon AH, Kieran MW, Beroukhim R , Ligon KL . Genomic analysis of diffuse pediatric low-grade gliomas identifies recurrent oncogenic truncating rearrangements in the transcription factor MYBL1. Proc Natl Acad Sci USA 2013 May 14; 110:8188-93.