Tumour genomics - Lauri Aaltonen
Our research revolves around genomics of benign and malignant tumours. The work scrutinises both hereditary and acquired genetic mutations and variations that can cause uncontrolled cell growth. The overall aim is to create, integrate, and interpret information on human tumourigenesis to facilitate cancer prevention, diagnosis, and treatment. At KI, our research team has so far focused on two types of tumours; uterine leiomyomas and colorectal cancer.
Uterine leiomyomas are extremely common benign tumours that arise from the smooth muscle layer of the uterus. Although benign they can cause a variety of symptoms such as excessive bleeding and abdominal pain, and negatively affect fertility and pregnancy.
Recent work from our research group at the University of Helsinki has revealed that although uterine leiomyomas are widely regarded a single entity, there are at least four distinct subgroups of leiomyomas with characteristic genetic driver mutations.
Using patient samples collected in collaboration with clinicians at Danderyds Sjukhus, we are now further characterizing the features of the identified subgroups and exploring if and how the subtype specific features may affect the tumour’s sensitivity to drug treatment.
Colorectal cancer is our long-term interest, and the group has contributed to several key discoveries along the way. Although a number of genetic variations (mutations) have been linked to colorectal cancer, we still do not know the full set of mutations that are necessary and together sufficient to cause this type of cancer. One of the aims with our research is to identify novel mutations/genetic aberrations that contribute to colorectal cancer and to explore how these contribute to tumourigenesis.
In a recent high-throughput effort to characterise structural genetic changes in a large number of human colorectal cancer samples (Palin et al. Nature Communications 2018), a set of plausible candidate targets were identified. We are currently functionally validating one of the most striking findings to see if and how the putative driver gene contributes to colorectal cancer.
Lauri Aaltonen is a Visiting Professor (Cancer Genetics) at KI, and his main position is at the University of Helsinki where he is the Director of the Center of Excellence in Tumour Genetics Research.
MED12 mutations and FH inactivation are mutually exclusive in uterine leiomyomas.
Kämpjärvi K, Mäkinen N, Mehine M, Välipakka S, Uimari O, Pitkänen E, et al
Br. J. Cancer 2016 06;114(12):1405-11
Integrated data analysis reveals uterine leiomyoma subtypes with distinct driver pathways and biomarkers.
Mehine M, Kaasinen E, Heinonen HR, Mäkinen N, Kämpjärvi K, Sarvilinna N, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 Feb;113(5):1315-20
Contribution of allelic imbalance to colorectal cancer.
Palin K, Pitkänen E, Turunen M, Sahu B, Pihlajamaa P, Kivioja T, et al
Nat Commun 2018 09;9(1):3664
Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans.
Kaasinen E, Kuismin O, Rajamäki K, Ristolainen H, Aavikko M, Kondelin J, et al
Nat Commun 2019 03;10(1):1252