Cartolano Lab
Dynamics of mutational processes in cancer
Our research focus:
The study of somatic alterations in cancer is pivotal to understand how tumors originate, progress and become resistant to therapy. Somatic mutations account for the genetic heterogeneity observed in clinical cancer specimens, thereby sculpting the architecture of tumor cell populations under the Darwinian laws of natural selection. Vulnerability of the DNA to damage is influenced by (epi)genomic features and tissue specific properties of the DNA repair machinery. Nevertheless, the exquisite specificity with which mutationalprocesses can mutate the DNA allows for the computational inference of their activity in whole genome and whole exome sequenced cancers.
Thus, the cancer mutation landscape is the result of the combination of specific mutational processes operating in a tissue dependent context. The inference of cancer-type specific mutational signatures, the study of their dynamic activity during cancer evolution and of their role in shaping the architecture of cancer cell populations is the object of our research.
Our goals:
Our goal is to understand the principles underlying cancer progression and therapy response.
We use patient-derived cancer cell lines to follow the evolving tumor population make up upon chemo and irradiation treatment. Observing tumor evolution in the making, we aim to identify cellular regulatory mechanisms relevant to tumor progression that can be harnessed with novel therapeutic strategies.
Our approach:
In order to understand how tumors grow and evolve in response to therapy, we perform functional studies on patient derived cell lines. Massive parallel sequencing and single cell profiling in combination with state of the art in house developed computational tools are used to infer evolving cancer cell populations and the dynamic processes that shape them both at the (epi)genomic and at the transcriptomic level.
Principal Investigator
Most important publications
- Ackermann S*, Cartolano M*, Hero B, Welte A, Kahlert Y, Roderwieser A, Bartenhagen C, Walter E, Gecht J, Kerschke L, Volland R, Menon R, Heuckmann JM, Gartlgruber M, Hartlieb S, Henrich KO, Okonechnikov K, Altmüller J, Nürnberg P, Lefever S, de Wilde B, Sand F, Ikram F, Rosswog C, Fischer J, Theissen J, Hertwig F, Singhi AD, Simon T, Vogel W, Perner S, Krug B, Schmidt M, Rahmann S, Achter V, Lang U, Vokuhl C, Ortmann M, Büttner R, Eggert A, Speleman F, O'Sullivan RJ, Thomas RK, Berthold F, Vandesompele J, Schramm A, Westermann F, Schulte JH, Peifer M, Fischer M. A mechanistic classification of clinical phenotypes in neuroblastoma. Science. 2018 Dec 7;362(6419):1165-1170. * equal contribution
- Rosswog C, Fassunke J, Ernst A, Schömig-Markiefka B, Merkelbach-Bruse S, Bartenhagen C, Cartolano M, Ackermann S, Theissen J, Blattner-Johnson M, Jones B, Schramm K, Altmüller J, Nürnberg P, Ortmann M, Berthold F, Peifer M, Büttner R, Westermann F, Schulte JH, Simon T, Hero B, Fischer M. Genomic ALK alterations in primary and relapsed neuroblastoma. Br J Cancer. 2023 Apr;128(8):1559-1571.
- Rosswog C, Bartenhagen C, Welte A, Kahlert Y, Hemstedt N, Lorenz W, Cartolano M, Ackermann S, Perner S, Vogel W, Altmüller J, Nürnberg P, Hertwig F, Göhring G, Lilienweiss E, Stütz AM, Korbel JO, Thomas RK, Peifer M, Fischer M. Chromothripsis followed by circular recombination drives oncogene amplification in human cancer. Nat Genet. 2021 Dec;53(12):1673-1685.
- Herling CD, Abedpour N, Weiss J, Schmitt A, Jachimowicz RD, Merkel O, Cartolano M, Oberbeck S, Mayer P, Berg V, Thomalla D, Kutsch N, Stiefelhagen M, Cramer P, Wendtner CM, Persigehl T, Saleh A, Altmüller J, Nürnberg P, Pallasch C, Achter V, Lang U, Eichhorst B, Castiglione R, Schäfer SC, Büttner R, Kreuzer KA, Reinhardt HC, Hallek M, Frenzel LP, Peifer M. Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia. Nat Commun. 2018 Feb 20;9(1):727.
- Cartolano M*, Abedpour N*, Achter V, Yang TP, Ackermann S, Fischer M, Peifer M. CaMuS: simultaneous fitting and de novo imputation of cancer mutational signature. Sci Rep. 2020 Nov 9;10(1):19316.
- Klein S, Quaas A, Noh KW, Cartolano M, Abedpour N, Mauch C, Quantius J, Reinhardt HC, Büttner R, Peifer M, Helbig D. Integrative Analysis of Pleomorphic Dermal Sarcomas Reveals Fibroblastic Differentiation and Susceptibility to Immunotherapy. Clin Cancer Res. 2020 Nov 1;26(21):5638-5645.
- Müller N, Lorenz C, Ostendorp J, Heisel FS, Friese UP, Cartolano M, Plenker D, Tumbrink H, Heimsoeth A, Baedeker P, Weiss J, Ortiz-Cuaran S, Büttner R, Peifer M, Thomas RK, Sos ML, Berg J, Brägelmann J. Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer. Cancer Res. 2023 Aug 1;83(15):2471-2479.
- Perne C, Peters S, Cartolano M, Horpaopan S, Grimm C, Altmüller J, Sommer AK, Hillmer AM, Thiele H, Odenthal M, Möslein G, Adam R, Sivalingam S, Kirfel J, Schweiger MR, Peifer M, Spier I, Aretz S. Variant profiling of colorectal adenomas from three patients of two families with MSH3-related adenomatous polyposis. PLoS One. 2021 Nov 29;16(11):e0259185.