Millions of people worldwide are diagnosed with cancer every year. Sometimes it can even occur in multiple members within the same family. This may be due to the exposure of the same environmental factors, shared lifestyles, or merely be a coincidence. On the other hand, cancer may also be hereditary, which leads to a higher risk of tumor diseases within a family and is present in at least 5-10 % of all tumor cases. In addition to the occurrence of the tumor disease in multiple family members, genetic tumor risk syndromes are generally characterized by an earlier age of onset and a higher likelihood of multiple cancers in an individual and in family members. Genetic testing can reveal the cause of a tumor risk syndrome in such cases and plays an important role for counseling of family members and assessing their tumor risk, recommending appropriate cancer screening or prophylactic surgery and individualized treatment options. However, with the current diagnostic methods, detecting the potential underlying genetic cause is not always possible.
Genetic Tumor Risk Syndromes
Figure1: To identify causative genetic variants that can explain recurrent cancers in a family, we use high throughput technologies to identify the changes in the patient’s DNA, RNA and proteins to correlate them to a phenotype. Functional and biological assays will help us to understand the pathogenicity of the identified variants. Subsequently, genetic testing can be offered for relatives and guides clinical recommendations. © A. Jahn /T.J. Widmann
Understanding “Genetic Tumor Risk Syndromes”
The group's goal is to discover unknown molecular causes of genetic tumor risk syndromes by studying DNA, as well as RNA and proteins generated from the genetic information (Figure 1). The complex analysis of various broad molecular characterizations using high-throughput technologies (omics) on healthy as well as tumor tissue-derived patient cells is part of the diagnostic workflow of the NCT/ DKTK-MASTER program, which is a multicenter prospective study investigating targeted therapy options in young tumor patients or patients with rare tumor diseases. Within this program, we assess genetic variants associated with hereditary tumor risk syndromes that may have direct clinical consequences (A. Jahn et al., Ann. Oncol., 2022). Our goal is to better understand the clinical consequences of human genetic variant assessment within precision oncology and to improve information transfer for patients with genetic tumor risk syndromes.
Figure 2: Genetic counseling provides the patient and their family with information about possible consequences of a genetic condition and genetic testing, such as individualized surveillance, preventive interventions or targeted drugs and recurrence risks. (c) University Hospital Dresden/Marc Eisele
In independent research projects, we are analyzing the pathogenicity of variants of unclear significance in tumor risk genes as well as variants in genes that may be associated with heritability. This involves the investigation of affected molecular signaling pathways and functional assays. In the long term, these different approaches could lead to improved diagnostic and possibly therapeutic options for patients with genetic tumor risk syndromes.
- DNA and RNA sequencing methods (in collaboration) and omics data analysis
- Variant evaluation for tumor risk genes and candidate genes
- Protein analysis (Western Blot, Immunoprecipitation, Immunocytochemistry, Reporter gene assays)
- Transfection, knockdown and overexpression, gene editing and functional analysis in cell culture models
Dr. Arne Jahn
Phone: +49 (0)351 458-14278
Dr. Thomas Widmann
Phone: +49 (0)351 458-12182
Dr. Andrès Cruz García
Phone: +49 (0)351 458-11950
Prospective PhD student
Phone: +49 (0)315 458-19598
Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers Jahn A, Rump A, Widmann T J, Heining C, Horak P, Hutter B, Paramasivam N, Uhrig S, Gieldon L, Drukewitz S, Kübler A, Bermudez M, Hackmann K, Porrmann J, Wagner J, Arlt M, Franke M, Fischer J, Kowalzyk Z, William D, Weth V, Oster S, Fröhlich M, Hüllein J, Orleś M, Valle González C, Kreutzfeldt S, Mock A, Heilig C E, Lipka D B, Möhrmann L, Hanf D, Teleanu V, Allgäuer M, Ruhnke L, Kutz O, Knurr A, Laßmann A, Endris V, Neumann O, Penzel R, Beck K , Richter D, Winter U, Wolf S, Pfütze , Geörg C, Meißburger B, Buchhalter I, Augustin M, Aulitzky W E, Hohenberger P, Kroiss M, Schirmacher P, Schlenk R F, Keilholz U, Klauschen F, Folprecht G, Bauer S, Siveke J T, Brandts C H, Kindler T, Boerries M, Illert A L, von Bubnoff N, Jost P J , Metzeler K H, Bitzer M, Schulze-Osthoff K, von Kalle C, Brors B , Stenzinger A, Weichert W, Hübschmann D, Fröhling S, Glimm H, Schröck E, Klink B. Ann Oncol. 2022 Aug 18;S0923-7534(22)01859-2. doi: 10.1016/j.annonc.2022.07.008
Comprehensive genomic and epigenomic analysis in cancer of unknown primary guides molecularly-informed therapies despite heterogeneity. Möhrmann L, Werner M, Oleś M, Mock A, Uhrig S, Jahn A, Kreutzfeldt S, Fröhlich M, Hutter B, Paramasivam N, Richter D, Beck K, Winter U, Pfütze K, Heilig CE, Teleanu V, Lipka DB, Zapatka M, Hanf D, List C, Allgäuer M, Penzel R, Rüter G, Jelas I, Hamacher R, Falkenhorst J, Wagner S, Brandts CH, Boerries M, Illert AL, Metzeler KH, Westphalen CB, Desuki A, Kindler T, Folprecht G, Weichert W, Brors B, Stenzinger A, Schröck E, Hübschmann D, Horak P, Heining C, Fröhling S, Glimm H. Nat Commun. 2022 Aug 2;13(1):4485. PMID: 35918329
Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers. Horak P, Heining C, Kreutzfeldt S, Hutter B, Mock A, Hullein J, Frohlich M, Uhrig S, Jahn A, Rump A, Gieldon L, Mohrmann L, Hanf D, Teleanu V, Heilig CE, Lipka DB, Allgauer M, Ruhnke L, Lassmann A, Endris V, Neumann O, Penzel R, Beck K, Richter D, Winter U, Wolf S, Pfutze K, Georg C, Meissburger B, Buchhalter I, Augustin M, Aulitzky WE, Hohenberger P, Kroiss M, Schirmacher P, Schlenk RF, Keilholz U, Klauschen F, Folprecht G, Bauer S, Siveke JT, Brandts CH, Kindler T, Boerries M, Illert AL, von Bubnoff N, Jost PJ, Spiekermann K, Bitzer M, Schulze-Osthoff K, von Kalle C, Klink B, Brors B, Stenzinger A, Schrock E, Hubschmann D, Weichert W, Glimm H, Frohling S. Cancer Discov. 2021 Jun 10:candisc.0126.2021. doi: 10.1158/2159-8290.CD-21-0126. PMID: 34112699.
Recommendation and Acceptance of Counselling for Familial Cancer Risk in Newly Diagnosed Breast Cancer Cases. Kast K, Häfner J, Schröck E, Jahn A, Werner C, Meisel C, Wimberger P. Breast Care 2021. doi: 10.1159/000517021
Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay. Souto Melo U, Bonner D, Kent Lloyd K C...Di Donato N, Jahn A, Chedrawi A, Alkuraya F S, Kok F, Byers H M. Genet Med. 2021 Jan 8. PMID: 33420346
The landscape of chromothripsis across adult cancer types. Voronina N, Wong JKL...Jahn A, ...Lichter P, Fröhling S, Ernst A. Nat Commun. 2020 May 8;11(1):2320. PMID: 32385320
Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease. Berger AK, Mughal SS, Allgäuer M, ... Jahn A, Schröck E, ...Stenzinger A, Fröhling S, Glimm H, Heining C. Pancreatology. 2020 Apr;20(3):425-432. PMID: 32156527
Optimizing Genetic Workup in Pheochromocytoma and Paraganglioma by Integrating Diagnostic and Research Approaches. Gieldon L, William D, Hackmann K, Jahn W, Jahn A, Wagner J, ... Schröck E, Eisenhofer G, Richter S, Klink B. Cancers (Basel). 2019 Jun 11;11(6). PMID: 31212687
Novel VPS33B mutation in a patient with autosomal recessive keratoderma-ichthyosis-deafness (ARKID) syndrome. Alter S, Hotz A, Jahn A, Di Donato N, ... Fischer J, Tzschach A.Am J Med Genet A. 2018 Dec;176(12):2862-2866. PMID: 30561130
Diagnostic value of partial exome sequencing in developmental disorders. Gieldon L, Mackenroth L, Kahlert AK, ... Jahn A, Kuhlee F, Hackmann K, Schrock E, Di Donato N, Rump A. PLoS One. 2018 Aug 9;13(8):e0201041. PMID: 30091983
Novel truncating PPM1D mutation in a patient with intellectual disability. Porrmann J, Rump A, Hackmann K, Di Donato N, Kahlert AK, Wagner J, Jahn A, Eger I, Flury M, Schrock E, Tzschach A, Gieldon L. Eur J Med Genet. 2018 May 11. pii: S1769-7212(18)30067-3. PMID: 29758292
ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator. Jahn A*, Rane G*, Paszkowski-Rogacz M, Sayols S, Bluhm A, Han CT, Draškovič I, Londoño-Vallejo JA, Kumar AP, Buchholz F, Butter F, Kappei D. EMBO Rep. 2017 Jun;18(6):929-946. PMID: 28500257 *These authors contributed equally to this work