Project C4
The fitness landscape of BRCA2 loss and therapy resistance across cancers
| 2022 – 2025 | Predicting molecular mechanisms of adaptation to chemoradiation therapy in cancer |
| 2018 – 2021 | Predicting patterns of adaptation to radio-chemotherapy in cancer |
It is still not fully understood why certain cancer-driving gene mutations occur mainly in specific tissues. For instance, inherited mutations in the genes BRCA1 and BRCA2—which impair DNA repair—often lead to breast and ovarian cancer and are treated with PARP inhibitors. This project will develop a model to understand how the loss of BRCA2 affects the growth and evolution of cancers in different tissue types. We hypothesize that BRCA2 loss has mixed effects: it may accelerate cancer evolution by increasing mutations, but it may also harm cells by causing genome instability and harmful genetic changes. To test this, we will study several cancer cell lines, analyze genetic data from more than 700 lung cancer patients, and examine how BRCA mutations influence treatment response. Ultimately, the project aims to improve predictions of treatment resistance and design combination therapies that reduce the chances that cancers evolve drug resistance.
Publications
enzel, M. C., Dasmeh, P., Plum, P. S., Giel, ..., & Hillmer, A. M, Cell Genomics, 5(10), 08. Sep 2025, 10.1016/j.xgen.2025.100980
Plum, P. S., Hess, T., Bertrand, D., Morgenstern, I., Velazquez Camacho, O., Jonas, C., Alidousty, C., Wagner, B., Roessler, S., Albrecht, T., Becker, J., Richartz, V., Holz, B., Hoppe, S., Poh, H. M., Chia, B. K. H., Chan, C. X., Pathiraja, T., Teo, A. S., … Hillmer, A. M., ROS1 fusion gene and PBX1 as prognostic marker, Clinical and Translational Medicine, 14(6), 14. Jun 2024, 10.1002/ctm2.1723
Why loss of Y? A pan-cancer genome analysis of tumors with loss of Y chromosome
Müller, P., Velazquez Camacho, O., Yazbeck, A. M., Wölwer, C., Zhai, W., Schumacher, J., Heider, D., Buettner, R., Quaas, A., & Hillmer, A. M, Computational and Structural Biotechnology Journal, 21, 15. Feb 2023, 10.1016/j.csbj.2023.02.024
Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma
Hoppe, S., Jonas, C., Wenzel, M. C., Velazquez Camacho, O., Arolt, C., Zhao, Y., Büttner, R., Quaas, A., Plum, P. S., & Hillmer, A. M, Cancers, 13(17), 26. Aug 2021, 10.3390/cancers13174300
Genomic Characterization of TP53–Wild-Type Esophageal Carcinoma1
Quaas A., Heydt C., Gebauer F., Alakus H., Loeser H., Büttner R., Hillmer A., Bruns C., Merkelbach-Bruse S., Zander T., Frommolt P., Transl Oncol., 12, 11. Oct 2018, 10.1016/j.tranon.2018.09.007
Kron A., Alidousty C., Scheffler M., Merkelbach-Bruse S., Seidel D., Riedel R., Ihle M. A., Michels S., Nogova L., Fassunke J., Heydt C., Kron F., Ueckeroth F., Serke M., Krüger S., Grohe C., Koschel D., Benedikter J., Kaminsky B., Schaaf B., Braess J., Sebastian M., Kambartel K. O., Thomas R., Zander T., Schultheis A. M., Büttner R., Wolf J., Ann Oncol., 29, 01. Oct 2018, 10.1093/annonc/mdy333
Alidousty C., Baar T., Martelotto L. G., Heydt C., Wagener S., Fassunke J., Duerbaum N., Scheel A. H., Frank S., Holz B., Binot E., Kron A., Merkelbach-Bruse S., Ihle M. A., Wolf J., Büttner R., Schultheis A.M., J Pathol., 246, 09. Jun 2018, 10.1002/path.5110
ATM Deficiency Is Associated with Sensitivity to PARP1- and ATR Inhibitors in Lung Adenocarcinoma
Schmitt A., Knittel G., Welcker D., Yang TP., George J., Nowak M., Leeser U., Büttner R., Perner S., Peifer M., Reinhardt HC., Cancer Res., 31. March 2017, 10.1158/0008-5472.CAN-16-3398
Jokić M., Vlašić I., Rinneburger M., Klümper N., Spiro J., Vogel W., Offermann A., Kümpers C., Fritz C., Schmitt A., Riabinska A., Wittersheim M., Michels S., Ozretić L., Florin A., Welcker D., Akyuz M.D., Nowak M., Erkel M., Wolf J., Büttner R., Schumacher B., Thomale J., Persigehl T., Maintz D., Perner S., Reinhardt H.C., Mol Cancer Res. Nov 14(11): 1110-1123, 11. August 2016, 10.1158/1541-7786.MCR-16-0094