Division of Molecular Genetic Epidemiology

Prof. Dr. Kari Hemminki

Genome-wide association study (Manhattan plot) on Hodgkin lymphone (Enciso-Mora et al. Nature Genet 2010). The strongest association with many SNPs is shown for the MHC complex on chromosome 6.
© dkfz.de

The three lines of our research include epidemiology and genetic basis of familial cancer, translational genomics of cancer and TERT promoter mutations in cancer. We have recently completed analysis of familial risks in non-Hodgkin lymphoma, Hodgkin disease, multiple myeloma and testicular cancer. Some extraordinary high familial risks suggest a strong genetic contribution. Sibling risk for Hodgkin disease was 6.0, and for the rare lymphocyte rich subtype it was 57. For testicular cancer the risk was increased over 20-fold if two or more family members were also diagnosed with this cancer. Myeloma showed intriguing associations with bone and connective tissue cancers. We sequence DNA from highly familial cases from Mendelian-type of cancer families in order to find novel predisposing genes. Such families have been identified through collaborators who have collected familial/hereditary cancers. The main focus has been on colorectal cancer.

The main translational project based on a genome-wide association study (GWAS) design is on multiple myeloma in collaboration with Hartmut Goldschmidt who heads the largest myeloma clinic in Germany. Most patients are recruited from clinical trials and GWAS data are available on 1800 patients, most also with cytogenetic (FISH) and gene expression data. The results on bone disease revealed an association with the osteoprotegerin gene, a negative regulator of bone resorption, and on survival an association with chromosome 6q25.1; homozygosity for the risk allele shortened median survival from 92 to 43 months.

Following our discovery of TERT promoter mutations it has become evident that these alterations are common somatic events in many cancers, being associated with adverse outcomes and thus provide prognostic information. For example in melanoma TERT promoter mutations were associated with increased patient age, increased Breslow thickness, tumor ulceration and tumor growth rate, all markers of poor prognosis. In melanoma and glioma we have unambiguously shown that TERT promoter mutations result in increased TERT expression. We are trying to understand the genetic events leading to transformation of benign nevi to advanced melanomas. The data will be informative of the driver genetic pathways and of defining the genetic architecture of melanoma.

For research on epidemiology and genetic basis of familial cancer we continue to deliver clinically useful risk prediction tools based on familial risk and individual patient characteristics. In genome-wide sequencing of samples from Mendelian-type of cancer families we aim at identifying novel high-to-moderate risk genes and characterize their population prevalence and risk profile. For translational genomics we search for susceptibility genes for cancers with focus on clinical relevance of germline events. In myeloma we have a possibility to test what therapeutic improvements individualized “omics” data will bring. Regarding TERT promoter mutations we will define how specific TERT promoter mutations influence clinical presentation, prognosis and therapeutic response of cancer. By genome-wide sequencing we want to follow the evolution of mutations in the course of transformation from benign nevi to advanced melanoma.


Prof. Dr. Kari Hemminki
Molecular Genetic Epidemiology (C050)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 580
69120 Heidelberg
Tel: +49 6221 42 1800

Selected Publications

  • Frank C, Fallah M, T. C, Mai EK, Sundquist J, Forsti A, et al. Search for familial clustering of multiple myeloma with any cancer Leukemia. 2016;30:627-32.
  • Johnson DC, Weinhold N, Mitchell J, Chen B, Stephens OW, Forsti A, et al. Genetic factors influencing the risk of multiple myeloma bone disease. Leukemia. 2016; 30:883-8.
  • Johnson DC, Weinhold N, Mitchell JS, Chen B, Kaiser M, Begum DB, et al. Genome-wide association study identifies variation at 6q25.1 associated with survival in multiple myeloma. Nature Communications. 2016;7:10290.
  • Nagore E, Heidenreich B, Rachakonda S, Garcia-Casado Z, Requena C, Soriano V, et al. TERT promoter mutations in melanoma survival. Int J Cancer. 2016;139:75-84.
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