Sarcoma Computational Biology Laboratory

Overview

The Sarcoma Computational Biology Laboratory is under the direction of Dimitrios Spentzos, MD, M.MSc. The laboratory collaborates with a number of oncology, radiation oncology, and pathology investigators at the Center for Sarcoma and Connective Tissue Oncology and the Mass General Brigham Cancer Institute. It also works closely with other Harvard Medical School research affiliates such as the Department of Data Sciences at the Dana Farber Cancer Institute, the Department of Biostatistics at the Harvard School of Public Health, and the Harvard Initiative for RNA Medicine (HIRM) and the Pediatric Oncology Program at Boston Children’s Hospital.

The mission of the lab is to uncover the mechanisms of tumor behavior and understand how they show different responses to conventional and novel treatments by studying genome-wide DNA, RNA, microRNA, and DNA methylation profiles and determining their relationship with biologic and clinical outcomes. We utilize microarray and deep sequencing platforms and advanced biostatistical and computational analyses methods to detect biologic and clinical signal in highly dimensional and often noisy genomic data. Our studies aim to develop molecular patterns that can function as biomarkers to guide treatment strategies and can also be used as functional “read outs” of response to therapy.

In addition, we are exploring novel molecular classification approaches to sarcomas based on genomic profiling, that can complement traditional histology-based classification, as it is recognized that if often does not capture the entire biologic diversity of sarcomas or their differential clinical response patterns. For example, novel insights into osteosarcoma subtypes may be gained by recent work on the role of a non-coding 14q32 chromosome-based cluster in osteosarcoma. Finally, in close collaboration with our computational biology and bioinformatics affiliate centers we are interested in assisting in the development and implementation of novel bioinformatics approaches to analyze highly dimensional genomic data in a clinically and biologically relevant manner.

Our lab has a track record of NIH funding and is also part of Cancer Institute efforts to utilize generous philanthropic contributions to cancer research at Mass General.

Research Projects

• Epigenetic (DNA methylation and microRNA) biomarkers of osteosarcoma outcome.
• Transcriptomic patterns of osteosarcoma progression and outcome.
• Non-coding RNA patterns in sarcomas.
• Genomic biomarkers of response to novel cancer treatments.
• Novel bioinformatics methodologies to assess clinically and biologically relevant patterns in highly dimensional genomic data.

Publications

• An international framework for clinical translation of molecular classifiers in osteosarcoma. Marinoff AE, Nathrath M, Shulman DS, Whittle SB, Pavisic J, Spentzos D, Albert CM, Nash JO, Shlien A, Cortés-Ciriano I, Marchais A, López-Fuentes E, Curtis C, Sweet-Cordero EA, Gorlick R, DelRocco N, Chugh R, Tap WD, Flanagan AM, Gaspar N, Crompton BD, Reed DR, Janeway KA, Grohar PJ, Livingston JA, Roberts RD. NPJ Precision Oncology, 2026, May 6
• Epigenetic patterns and methylation-based models for robust outcome prediction in osteosarcoma. Joshua J. Bowers, Nikhil Ramavenkat, Christopher E. Lietz, Miya Hugaboom, Aditya Madupur, Edwin Choy, Gregory M. Cote, Martin J. Aryee, Dimitrios Spentzos. medRxiv 2025.11.19.25340108; doi: https://doi.org/10.1101/2025.11.19.25340108.
• Adjuvant chemotherapy in localized, resectable extremity and truncal soft tissue sarcoma and survival outcomes - A systematic review and meta-analysis of randomized controlled trials. Goh MH, Gonzalez MR, Heiling HM, Mazzola E, Connolly JJ, Choy E, Cote GM, Spentzos D, Lozano-Calderon SA. Cancer. 2025 Mar 1;131(5):e35792. doi: 10.1002/cncr.35792. PMID: 40023772.
• A dynamic microRNA profile that tracks a chemotherapy resistance phenotype in osteosarcoma. Implications for novel therapeutics. Lietz CE, Newman ET, Kelly AD, Xiang DH, Zhang Z, Ramavenkat N, Bowers JJ, Lozano-Calderon SA, Ebb DH, Raskin KA, Cote GM, Choy E, Nielsen GP, Vlachos IS, Haibe-Kains B, Spentzos D. medRxiv [Preprint]. 2024 Jun 20:2024.06.19.24309087. doi: 10.1101/2024.06.19.24309087. PMID: 38946948 Free PMC article.
• Complete tumor necrosis after neoadjuvant chemotherapy defines good responders in patients with Ewing sarcoma. Lozano-Calderón SA, Albergo JI, Groot OQ, Merchan NA, El Abiad JM, Salinas V, Gomez Mier LC, Montoya CS, Ferrone ML, Ready JE, Linares FJ, Levin AS, Peleteiro Pensado M, Pozo Kreilinger JJ, Ruiz IB, Ortiz-Cruz EJ, Gebhardt MC, Cote GM, Choy E, Spentzos D, Hung YP, Deshpande V, Chebib IA, McCulloch RA, Farfalli G, Aponte Tinao L, Morris CD, Petur Nielsen G, Anderson ME, Jeys LM. Cancer. 2023 Jan 1;129(1):60-70. doi: 10.1002/cncr.34506. Epub 2022 Oct 28. PMID: 36305090.
• Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma. Wei Y, Qin Q, Yan C, Hayes MN, Garcia SP, Xi H, Do D, Jin AH, Eng TC, McCarthy KM, Adhikari A, Onozato ML, Spentzos D, Neilsen GP, Iafrate AJ, Wexler LH, Pyle AD, Suvà ML, Dela Cruz F, Pinello L, Langenau DM.
• Nat Cancer. 2022 Aug;3(8):961-975. doi: 10.1038/s43018-022-00414-w. Epub 2022 Aug 18. PMID: 35982179.
• EWSR1-ATF1 dependent 3D connectivity regulates oncogenic and differentiation programs in Clear Cell Sarcoma.
• Möller E, Praz V, Rajendran S, Dong R, Cauderay A, Xing YH, Lee L, Fusco C, Broye LC, Cironi L, Iyer S, Rengarajan S, Awad ME, Naigles B, Letovanec I, Ormas N, Finzi G, La Rosa S, Sessa F, Chebib I, Petur Nielsen G, Digklia A, Spentzos D, Cote GM, Choy E, Aryee.
• M, Stamenkovic I, Boulay G, Rivera MN, Riggi N. Nat Commun. 2022 Apr 27;13(1):2267. doi: 10.1038/s41467-022-29910-4. PMID: 35477713.
• Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma.
• Lietz CE, Newman ET, Kelly AD, Xiang DH, Zhang Z, Luscko CA, Lozano-Calderon SA, Ebb DH, Raskin KA, Cote GM, Choy E, Nielsen GP, Haibe-Kains B, Aryee MJ, Spentzos D. Commun Biol. 2022 Mar 8;5(1):213. doi: 10.1038/s42003-022-03117-1.

Open Positions

The laboratory generally employs research assistants with a clear academic orientation, who typically move on to graduate (PhD, MD, or MD/PhD) studies, and we are in the process of expanding with new and higher-level post graduate positions. In addition, we provide mentorship to undergraduate and graduate students who are interested to participate in our research. Contact Dimitris Spentzos, MD, to learn more: dspentzos@mgh.harvard.edu