Research

INTERNATIONAL LYNCH SYNDROME RESEARCH

Inherited MMR deficiency, i.e. Lynch syndrome, gives rise to a broad spectrum of tumors, especially colorectal and endometrial cancers, but also ovarian, gastric, urinary, small bowel, brain and bile duct/gallbladder cancers. The history of international Lynch syndrome research can be traced back to 1895 and the discovery of a family cancer syndrome. The disease was characterized by Henry T. Lynch in 1966 and came to be known as Hereditary NonPolyposis Colorectal Cancer (HNPCC), which in honour of Dr. Lynch’s findings, was later termed Lynch syndrome. The molecular genetics era began in 1993 when a germline MMR gene mutation was identified as a cause of LS. Currently Lynch syndrome research is being actively carried out worldwide, with an approach that focuses on obtaining a deeper understanding of the molecular mechanism behind LS, enabling preventive diagnosis and personalized medical care.

RESOURCES

International Society for Gastrointestinal Hereditary Tumors (InSiGHT) is an international multidisciplinary, scientific organization with the mission to improve the quality of care of patients and their families with any condition resulting in hereditary gastrointestinal tumors. The inventors, scientific advisors, key collaborators, and LS CancerDiag Ltd employees have actively participated in the activities of InSiGHT.

Finnish HNPCC is a group formed by leading Finnish Lynch syndrome researchers. The group is actively involved in several projects on the MMR mechanism and LS in collaboration with Central University Hospitals in Finland.

International Agency for Cancer Research (IARC) is the specialized cancer agency of the World Health Organization. The objective of the IARC is to promote international collaboration in cancer research to adopt preventive measures and reduce cancer mortality.

ACADEMIC RESEARCH ROOT OF DIAGMMR®

The DiagMMR® innovation is based on more than 20 years of academic research at the University of Helsinki, where the functional MMR assay research and development has resulted in 7 PhDs and 30 original peer-reviewed publications in the 2000’s. DiagMMR® is an advanced application of an in vitro MMR assay used for the functional characterization of MMR gene mutations.

PUBLICATIONS

Kasela M, Nyström M, Kansikas M. (2019) PMS2 expression decrease causes severe problems in mismatch repair. Hum Mutat 40(7):904-907.

Tricarico R, Kasela M, Mareni C, Thompson BA, Drouet A, Staderini L, Gorelli G, Crucianelli F, Ingrosso V, Kantelinen J, Papi L, De Angioletti M, Berardi M, Gaildrat P, Soukarieh O, Turchetti D, Martins A, Spurdle AB, Nyström M, Genuardi M; InSiGHT Variant Interpretation Committee (2017) Assessment of the InSiGHT Interpretation Criteria for the Clinical Classification of 24 MLH1 and MSH2 Gene Variants. Hum Mutat 38(1):64-77.

Nyström, M. & Kansikas, M. (2017) Predictive cancer diagnostics: LS CancerDiag Ltd has developed DiagMMR, an innovative method to detect cancer syndrome before cancers form. Pan European Networks, Health 02:164-165.

Kansikas, M., Kasela, M., Kantelinen, J. & Nyström, M. (2014) Assessing How Reduced Expression Levels of the Mismatch Repair Genes MLH1, MSH2, and MSH6 Affect Repair Efficiency. Human Mutation, 35:1123-1127.

Nyström, M. & Kansikas, M. (2013) DNA Alterations in Lynch Syndrome. Functional Analyses Help to Assess the Pathogenicity of MMR Gene Variants of Uncertain Significance. DNA Alterations in Lynch Syndrome: Advances in molecular diagnosis and genetic counseling. Vogelsang, M. (ed.). Springer, p. 85-100.

Kansikas, M., Kariola, R. & Nyström, M. (2011) Verification of the Three-Step Model in Assessing the Pathogenicity of Mismatch Repair Gene Variants. Human Mutation, 32:107-115.

Ollila, S., Sarantaus, L., Kariola, R., Chan, P., Hampel, H., Holinski-Feder, E., Macrae, F., Kohonen-Corish, M., Gerdes, A.M., Peltomäki, P., Mangold, E., de la Chapelle, A., Greenblatt, M. & Nyström, M. (2006) Pathogenicity of MSH2 missense mutations is typically associated with impaired repair capability of the mutated protein. Gastroenterology, 131:1408-1417.

Raevaara T.E., Korhonen M.K., Lohi H., Hampel H., Lynch E., Lönnqvist K.E., Holinski-Feder E., Sutter C., McKinnon W., Duraisamy S., Gerdes A.M., Peltomäki P., Kohonen-Ccorish M., Mangold E., Macrae F., Greenblatt M., de la Chapelle A., Nyström M. (2005) Functional significance and clinical phenotype of nontruncating mismatch repair variants of MLH1. Gastroenterology, 129:537-49.