Browsing by Author "Michor, Franziska"
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(A)Symmetric Stem Cell Replication and Cancer
Dingli, David; Traulsen, Arne; Michor, Franziska L. (Public Library of Science, 2007)Most tissues in metazoans undergo continuous turnover due to cell death or epithelial shedding. Since cellular replication is associated with an inherent risk of mutagenesis, tissues are maintained by a small group of stem ... -
ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
Wee, Boyoung; Pietras, Alexander; Ozawa, Tatsuya; Bazzoli, Elena; Podlaha, Ondrej; Antczak, Christophe; Westermark, Bengt; Nelander, Sven; Uhrbom, Lene; Forsberg-Nilsson, Karin; Djaballah, Hakim; Michor, Franziska; Holland, Eric C. (Nature Publishing Group, 2016)Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 ... -
Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity
De, Subhajyoti; Shaknovich, Rita; Riester, Markus; Elemento, Olivier; Geng, Huimin; Kormaksson, Matthias; Jiang, Yanwen; Woolcock, Bruce; Johnson, Nathalie; Polo, Jose M.; Cerchietti, Leandro; Gascoyne, Randy D.; Melnick, Ari; Michor, Franziska L. (Public Library of Science, 2013)Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation in normal ... -
Analysis of Somatic Microsatellite Indels Identifies Driver Events in Human Tumors
Maruvka, Yosef; Mouw, Kent; Karlic, Rosa; Parasuraman, Prasanna; Kamburov, Atanas; Polak, Paz; Haradhvala, Nicholas; Hess, Julian; Rheinbay, Esther; Brody, Yehuda; Koren, Amnon; Braunstein, Lior; D'Andrea, Alan; Lawrence, Michael; Bass, Adam; Bernards, Andre; Michor, Franziska; Getz, Gad (Springer Science and Business Media LLC, 2017-09-11)Microsatellites (MSs) are tracts of variable-length repeats of short DNA motifs that exhibit high rates of mutation in the form of insertions or deletions (indels) of the repeated motif. Despite their prevalence, the ... -
Breast Tumours Maintain a Reservoir of Subclonal Diversity During Expansion
Minussi, Darlan C.; Nicholson, Michael; Ye, Hanghui; Davis, Alexander; Wang, Kaile; Baker, Toby; Tarabichi, Maxime; Sei, Emi; Du, Haowei; Rabbani, Mashiat; Peng, Cheng; Hu, Min; Bai, Shanshan; Lin, Yu-wei; Schalck, Aislyn; Multani, Asha; Ma, Jin; McDonald, Thomas; Casasent, Anna; Barrera, Angelica; Chen, Hui; Lim, Bora; Arun, Banu; Meric-Bernstam, Funda; Van Loo, Peter; Michor, Franziska; Navin, Nicholas E. (Springer Science and Business Media LLC, 2021-03-24)Our knowledge of copy number evolution during the expansion of primary breast tumors is limited. To investigate this process, we developed a single cell, single-molecule DNA sequencing method and performed copy number ... -
Clonal Evolution in Breast Cancer Revealed by Single Nucleus Genome Sequencing
Wang, Yong; Waters, Jill; Leung, Marco L.; Unruh, Anna; Roh, Whijae; Shi, Xiuqing; Chen, Ken; Scheet, Paul; Vattathil, Selina; Liang, Han; Multani, Asha; Zhang, Hong; Zhao, Rui; Michor, Franziska; Meric-Bernstam, Funda; Navin, Nicholas E. (2014)SUMMARY Sequencing studies of breast tumor cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumors. Here, we developed a whole-genome and exome single cell ... -
DNA replication timing and higher-order nuclear organization determine single nucleotide substitution patterns in cancer genomes
Liu, Lin; De, Subhajyoti; Michor, Franziska (2013)Single nucleotide substitutions (SNS) are a defining characteristic of cancer genomes. Many SNS in cancer genomes arise due to errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA ... -
Dose-Dependent Mutation Rates Determine Optimum Erlotinib Dosing Strategies for EGFR Mutant Non-Small Cell Lung Cancer Patients
Liu, Lin L.; Li, Fei; Pao, William; Michor, Franziska (Public Library of Science, 2015)Background: The advent of targeted therapy for cancer treatment has brought about a paradigm shift in the clinical management of human malignancies. Agents such as erlotinib used for EGFR-mutant non-small cell lung cancer ... -
An Evolutionary Approach for Identifying Driver Mutations in Colorectal Cancer
Foo, Jasmine; Liu, Lin L; Leder, Kevin; Riester, Markus; Iwasa, Yoh; Lengauer, Christoph; Michor, Franziska (Public Library of Science, 2015)The traditional view of cancer as a genetic disease that can successfully be treated with drugs targeting mutant onco-proteins has motivated whole-genome sequencing efforts in many human cancer types. However, only a subset ... -
Evolutionary Dynamics of Intratumor Heterogeneity
Iwasa, Yoh; Michor, Franziska L. (Public Library of Science, 2011)Intraneoplastic diversity in human tumors is a widespread phenomenon of critical importance for tumor progression and the response to therapeutic intervention. Insights into the evolutionary events that control tumor ... -
FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder
Guancial, Elizabeth A; Werner, Lillian; Bellmunt, Joaquim; Bamias, Aristotle; Choueiri, Toni K; Ross, Robert; Schutz, Fabio A; Park, Rachel S; O'Brien, Robert J; Hirsch, Michelle S; Barletta, Justine A; Berman, David M; Lis, Rosina; Loda, Massimo; Stack, Edward C; Garraway, Levi A; Riester, Markus; Michor, Franziska; Kantoff, Philip W; Rosenberg, Jonathan E (BlackWell Publishing Ltd, 2014)While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive ... -
Histone Modifications Are Associated with Transcript Isoform Diversity in Normal and Cancer Cells
Podlaha, Ondrej; De, Subhajyoti; Gonen, Mithat; Michor, Franziska (Public Library of Science, 2014)Mechanisms that generate transcript diversity are of fundamental importance in eukaryotes. Although a large fraction of human protein-coding genes and lincRNAs produce more than one mRNA isoform each, the regulation of ... -
The Impact of Microenvironmental Heterogeneity on the Evolution of Drug Resistance in Cancer Cells
Mumenthaler, Shannon M; Foo, Jasmine; Choi, Nathan C; Heise, Nicholas; Leder, Kevin; Agus, David B; Pao, William; Michor, Franziska; Mallick, Parag (Libertas Academica, 2015)Therapeutic resistance arises as a result of evolutionary processes driven by dynamic feedback between a heterogeneous cell population and environmental selective pressures. Previous studies have suggested that mutations ... -
In situ single cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2+ breast cancer
Janiszewska, Michalina; Liu, Lin; Almendro, Vanessa; Kuang, Yanan; Paweletz, Cloud; Sakr, Rita A.; Weigelt, Britta; Hanker, Ariella B.; Chandarlapaty, Sarat; King, Tari A.; Reis-Filho, Jorge S.; Arteaga, Carlos L.; Park, So Yeon; Michor, Franziska; Polyak, Kornelia (2015)Detection of minor genetically distinct subpopulations within tumors is a key challenge in cancer genomics. Here we report STAR-FISH (Specific-To-Allele PCR – FISH), a novel method for the combined detection of single ... -
A Mathematical Methodology for Determining the Temporal Order of Pathway Alterations Arising during Gliomagenesis
Cheng, Yu-Kang; Beroukhim, Rameen; Levine, Ross L.; Mellinghoff, Ingo K.; Holland, Eric C.; Michor, Franziska L. (Public Library of Science, 2012)Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and thus represent ... -
Mathematical Modeling of Cancer Metastasis for Optimal Treatment Strategies
Ni, Peiyun (2016-06-30)Cancer is a leading cause of death in the world and becomes clinically incurable largely due to tumor metastasis. It therefore becomes important to understand the evolution of metastasis in order to determine optimal ... -
Mathematical Modeling of Erythrocyte Chimerism Informs Genetic Intervention Strategies for Sickle Cell Disease
Brendel, Christian; Renella, Raffaele; Michor, Franziska; Altrock, Philipp; Orkin, Stuart; Williams, David (Wiley, 2016-07-14)Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), a heritable disorder caused by a point mutation in the beta-globin gene. The developmental ... -
Non-cell autonomous tumor-growth driving supports sub-clonal heterogeneity
Marusyk, Andriy; Tabassum, Doris P.; Altrock, Philipp M.; Almendro, Vanessa; Michor, Franziska; Polyak, Kornelia (2014)SUMMARY Cancers arise through a process of somatic evolution that can result in substantial sub-clonal heterogeneity within tumors. The mechanisms responsible for the coexistence of distinct sub-clones and the biological ... -
On the Validity of Using Increases in 5-Year Survival Rates to Measure Success in the Fight against Cancer
Maruvka, Yosef E.; Tang, Min; Michor, Franziska (Public Library of Science, 2014)Background: The 5-year survival rate of cancer patients is the most commonly used statistic to reflect improvements in the war against cancer. This idea, however, was refuted based on an analysis showing that changes in ... -
Patterns of Proliferative Activity in the Colonic Crypt Determine Crypt Stability and Rates of Somatic Evolution
Zhao, Rui; Michor, Franziska (Public Library of Science, 2013)Epithelial cells in the colon are arranged in cylindrical structures called crypts in which cellular proliferation and migration are tightly regulated. We hypothesized that the proliferation patterns of cells may determine ...