Sandeep Dave

Positions:

Professor of Medicine

Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1999

Northwestern University

Medical Resident, Medicine

Northwestern University

Fellow in Hematology-Oncology, Medicine

National Institutes of Health

Grants:

Clinico-Genomic Assessment of Performance Status in Elderly AML Patients

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

Genetic and genomic signatures of long-term radiation exposure in non-human primates

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Wake Forest University School Of Medicine
Role
Principal Investigator
Start Date
End Date

Understanding the context-dependent roles of mutations in lymphoma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Phase 1 Trial of Panobinostat + Ruxolitnib for Relapsed/Refactory Diffused Large B Cell Lymphoma (DLBCL)

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
Lymphoma Research Foundation of America
Role
Mentor
Start Date
End Date

Understanding the Context-Dependent Roles of Mutations in Lymphoma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Genome-defined African ancestry is associated with distinct mutations and worse survival in patients with diffuse large B-cell lymphoma.

BACKGROUND: Significant racial differences have been observed in the incidence and clinical outcomes of diffuse large B-cell lymphoma (DLBCL) in the United States, but to the authors' knowledge it remains unclear whether genomic differences contribute to these disparities. METHODS: To understand the influences of genetic ancestry on tumor genomic alterations, the authors estimated the genetic ancestry of 1001 previously described patients with DLBCL using unsupervised model-based Admixture global ancestry analysis applied to exome sequencing data and examined the mutational profile of 150 DLBCL driver genes in tumors obtained from this cohort. RESULTS: Global ancestry prediction identified 619 patients with >90% European ancestry, 81 patients with >90% African ancestry, and 50 patients with >90% Asian ancestry. Compared with patients with DLBCL with European ancestry, patients with African ancestry were aged >10 years younger at the time of diagnosis and were more likely to present with B symptoms, elevated serum lactate dehydrogenase, extranodal disease, and advanced stage disease. Patients with African ancestry demonstrated worse overall survival compared with patients with European ancestry (median, 4.9 years vs 8.8 years; P = .04). Recurrent mutations of MLL2 (KMT2D), HIST1H1E, MYD88, BCL2, and PIM1 were found across all ancestry groups, suggesting shared mechanisms underlying tumor biology. The authors also identified 6 DLBCL driver genes that were more commonly mutated in patients with African ancestry compared with patients with European ancestry: ATM (21.0% vs 7.75%; P < .001), MGA (19.7% vs 5.33%; P < .001), SETD2 (17.3% vs 5.17%; P < .001), TET2 (12.3% vs 5.82%; P = .029), MLL3 (KMT2C) (11.1% vs 4.36%; P = .013), and DNMT3A (11.1% vs 4.52%; P = .016). CONCLUSIONS: Distinct prevalence and patterns of mutation highlight an important difference in the mutational landscapes of DLBCL arising in different ancestry groups. To the authors' knowledge, the results of the current study provide the first-ever characterization of genetic alterations among patients with African descent who are diagnosed with DLBCL.
Authors
Lee, MJ; Koff, JL; Switchenko, JM; Jhaney, CI; Harkins, RA; Patel, SP; Dave, SS; Flowers, CR
MLA Citation
Lee, Michelle J., et al. “Genome-defined African ancestry is associated with distinct mutations and worse survival in patients with diffuse large B-cell lymphoma.Cancer, vol. 126, no. 15, Aug. 2020, pp. 3493–503. Pubmed, doi:10.1002/cncr.32866.
URI
https://scholars.duke.edu/individual/pub1443342
PMID
32469082
Source
pubmed
Published In
Cancer
Volume
126
Published Date
Start Page
3493
End Page
3503
DOI
10.1002/cncr.32866

Identifying transcriptional profiles and evaluating prognostic biomarkers of HIV-associated diffuse large B-cell lymphoma from Malawi.

Lymphoma incidence in sub-Saharan Africa (SSA) is increasing due to HIV and population aging. Diffuse Large B-cell lymphoma (DLBCL), the most common lymphoma in SSA and worldwide, is highly associated with HIV, but molecular studies of HIV-associated DLBCL are scarce globally. We describe profiling of DLBCL from Malawi, aiming to elucidate tumor biology and identify clinically meaningful biomarkers specifically for SSA. Between June 1, 2013 and June 1, 2016, 59 cases of DLBCL (32 HIV+/27 HIV-) enrolled in the Kamuzu Central Hospital Lymphoma Study were characterized, of which 54 (92%) were negative for Epstein-Barr virus. Gene expression profiling (GEP) by whole transcriptome sequencing was performed on the first 36 cases (22 HIV+/14 HIV-). Immunohistochemistry (IHC) and GEP results were compared with published data and correlated to clinical outcome and pathologic features. Unsupervised clustering strongly segregated DLBCL by HIV status (p = 0.0003, Chi-squared test), indicating a marked contribution of HIV to expression phenotype. Pathway analysis identified that HIV-associated tumors were enriched in hypoxia, oxidative stress, and metabolism related gene expression patterns. Cell-of-origin subtype, determined by sequencing and IHC, did not associate with differences in overall survival (OS), while Ki-67 proliferation index ≥80% was associated with inferior OS in HIV+ DLBCL only (p = 0.03) and cMYC/BCL2 co-expression by IHC was negatively prognostic across the entire cohort (p = 0.01). This study provides among the first molecular characterizations of DLBCL from SSA, demonstrates marked gene expression differences by HIV status, and identifies genomic and immunophenotypic characteristics that can inform future basic and clinical investigations.
Authors
Fedoriw, Y; Selitsky, S; Montgomery, ND; Kendall, SM; Richards, KL; Du, W; Tomoka, T; Mulenga, M; Parker, JS; Dave, SS; Gopal, S
MLA Citation
Fedoriw, Yuri, et al. “Identifying transcriptional profiles and evaluating prognostic biomarkers of HIV-associated diffuse large B-cell lymphoma from Malawi.Mod Pathol, vol. 33, no. 8, Aug. 2020, pp. 1482–91. Pubmed, doi:10.1038/s41379-020-0506-3.
URI
https://scholars.duke.edu/individual/pub1433143
PMID
32080349
Source
pubmed
Published In
Modern Pathology
Volume
33
Published Date
Start Page
1482
End Page
1491
DOI
10.1038/s41379-020-0506-3

Polatuzumab Vedotin: Honing in on Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Authors
Shingleton, JR; Dave, SS
MLA Citation
Shingleton, Jennifer R., and Sandeep S. Dave. “Polatuzumab Vedotin: Honing in on Relapsed or Refractory Diffuse Large B-Cell Lymphoma.J Clin Oncol, vol. 38, no. 2, Jan. 2020, pp. 166–68. Pubmed, doi:10.1200/JCO.19.02587.
URI
https://scholars.duke.edu/individual/pub1422359
PMID
31770050
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
38
Published Date
Start Page
166
End Page
168
DOI
10.1200/JCO.19.02587

The whole-genome landscape of Burkitt lymphoma subtypes.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
Authors
Panea, RI; Love, CL; Shingleton, JR; Reddy, A; Bailey, JA; Moormann, AM; Otieno, JA; Ong'echa, JM; Oduor, CI; Schroeder, KMS; Masalu, N; Chao, NJ; Agajanian, M; Major, MB; Fedoriw, Y; Richards, KL; Rymkiewicz, G; Miles, RR; Alobeid, B; Bhagat, G; Flowers, CR; Ondrejka, SL; Hsi, ED; Choi, WWL; Au-Yeung, RKH; Hartmann, W; Lenz, G; Meyerson, H; Lin, Y-Y; Zhuang, Y; Luftig, MA; Waldrop, A; Dave, T; Thakkar, D; Sahay, H; Li, G; Palus, BC; Seshadri, V; Kim, SY; Gascoyne, RD; Levy, S; Mukhopadyay, M; Dunson, DB; Dave, SS
MLA Citation
Panea, Razvan I., et al. “The whole-genome landscape of Burkitt lymphoma subtypes.Blood, vol. 134, no. 19, Nov. 2019, pp. 1598–607. Pubmed, doi:10.1182/blood.2019001880.
URI
https://scholars.duke.edu/individual/pub1415067
PMID
31558468
Source
pubmed
Published In
Blood
Volume
134
Published Date
Start Page
1598
End Page
1607
DOI
10.1182/blood.2019001880

Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma.

DISCLOSURES: Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.
Authors
Li, X; Kositsky, R; Reddy, A; Love, C; Naresh, K; Koff, JL; Nystrand, I; Leppä, S; Pasanen, A; Karjalainen-Lindsberg, M-L; Dunkel, J; Kovanen, P; Qin, Q; Bhagat, G; Leeman-Neill, RJ; Goswami, RS; Wildeman, S; Delabie, J; Burack, R; Evans, AG; Amador, C; Yuan, J; Qureishi, HN; Li, S; Xu, J; Yin, CC; Gang, AO; Norgaard, PH; Pedersen, MØ; Chan, JY; Cheah, DMZ; Ong, SY; Cheng, CL; Lee, L; Paulua, F; Ondrejka, SL; Hsi, ED; Czader, M; Wang, L; Landis, A; Churnetski, MC; Jaye, DL; Flowers, CR; McCall, CM; Neff, J; McKinney, MS; Fedoriw, Y; Powers, E; Montgomery, ND; Bogusz, AM; Stafford Hintz, A; Kovach, AE; Reddy, N; Thompson Arildsen, MA; Mason, EF; Juskevicius, R; Choi, W; Au-Yeung, R; Tse, E; Sarno, V; Chadburn, A; Lopez, R; Chapman, JR; Behdad, A; Goldschmidt, N; Goodlad, J; Burton, C; Pillai, R; Louissaint, A; Soliman, DS; Panea, R; Dave, T; Xiong, B; Smith, E; Dave, S
MLA Citation
Li, Xiang, et al. “Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma.Blood, vol. 134, no. Supplement_1, Nov. 2019, p. 19. Pubmed, doi:10.1182/blood-2019-130255.
URI
https://scholars.duke.edu/individual/pub1421345
PMID
31723982
Source
pubmed
Published In
Blood
Volume
134
Published Date
Start Page
19
DOI
10.1182/blood-2019-130255