Clinical Genetics of Familial Cancer

Introduction

We are studying the genetic background of the familial clustering of cancer through whole genome sequencing and other techniques. We are interested in finding new genes, investigating the yield of existing detection strategies, and the clinical interpretation of missense and other types of variants that are difficult to classify clinically. Risk figures and clinical strategies are also being studied.

We are involved in a range of national and international studies, many of them focus on Lynch syndrome, the most common type of hereditary colorectal cancer, but also on other types of cancer.

Team members

Prof. Rolf Sijmons, MD, PhD (principal investigator, clinical geneticist)
Helga Westers, PhD (assistant professor)
Klaas Kok, PhD (assistant professor)
Mirjam de Jong, MD, PhD (clinical geneticist)
plus PhD students and lab technicians

-National collaborations

There is strong collaboration within the UMCG with the Departments of Gastroenterology, Pathology, Endocrinology, Surgery and Gynaecology, but also with
Dr. Niels de Wind, LUMC Leiden
Prof. Robert Hofstra, Erasmus MC, Rotterdam
Prof. Hein te Riele, NKI, Amsterdam
Prof. Nicoline Hoogerbrugge, Radboud MC, Nijmegen

-International collaborations

Prof. L.J. Ramussen, Roskilde University, Denmark
Dr. Marc Greenblatt, Burlington, USA
Prof. Sean Tavtigian, Utah, USA
Prof Rodney Scott, Newcastle, Australia
Prof. Kari Hemminki, DKFZ, Heidelberg, Germany
Prof. Jan Lubinski, Stettin, Poland
The Mallorca (“European InSiGHT”) Group on Lynch syndrome (Paul Moller and colleagues)

Recent papers
Sijmons RH, Hofstra RM. Clinical aspects of hereditary DNA mismatch repair gene mutations. DNA Repair (Amst). 2016;38:155-62

Johansson LF et al. CoNVaDING: Single exon variation detection in targeted NGS data. Hum Mutat. 2016;37(5):457-64. doi: 10.1002/humu.22969.

Møller P et al. (http://mallorca-group.org) Incidence of and survival after subsequent cancers in carriers of pathogenic MMR variants with previous cancer: a report from the prospective Lynch syndrome database. Gut. 2016. doi: 10.1136/gutjnl-2016-311403.

Møller P et al. (http://mallorca-group.eu) Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database. Gut. 2015 doi: 10.1136/gutjnl-2015-309675.

Nielsen M, ten Broeke S, Sijmons R. ClinGen and genetic testing. N Engl J Med. 2015;373(14):1377

Pang C et al. SORTA: a system for ontology-based re-coding and technical annotation of biomedical phenotype data. Database (Oxford). 2015;2015. pii: bav089. doi: 10.1093/database/bav089. Print 2015

Van der Velde KJ et al. InSiGHT GroupEvaluation of CADD Scores in Curated Mismatch Repair Gene Variants Yields a Model for Clinical Validation and Prioritization. Hum Mutat. 2015;36(7):712-9.

Ten Broeke SW et al. Lynch syndrome caused by germline PMS2 mutations: delineating the cancer risk. J Clin Oncol. 2015;33(4):319-25

Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists. Menko FH, Aalfs CM, Henneman L, Stol Y, Wijdenes M, Otten E, Ploegmakers MM, Legemaate J, Smets EM, de Wert GM, Tibben A; Dutch Society for Clinical Genetics. Fam Cancer. 2013;12(2):319-24. doi: 10.1007/s10689-013-9636-9