FCBT’s research projects 2021

Immunodeficiency in cartilage-hair hypoplasia: correlation with pulmonary disease, infections and malignancy

Svetlana Vakkilainen and Outi Mäkitie, University of Helsinki

Cartilage-hair hypoplasia (CHH) is a disease of the defense system and skeleton and it is exceptionally common in Finland. CHH patients have a higher risk of developing cancer, especially lymph node and skin cancer. Little is known about cancers in CHH patients. Various viruses have been linked to the onset of this cancer, but the role of these viruses in the development of cancers in CHH patients has not been studied. Genetic alterations leading to cancer in CHH patients are also unknown. This project investigates the presence of different viruses as well as the cancer gene in tumor samples from CHH patients with cancer. Our results increase knowledge of the underlying mechanisms of the defense system disorder and cancer and provide an evidence-based approach to patient care and follow-up.

Immune cell characterization of individuals infected by Sars-CoV-2

Zhi Chen, University of Oulu

Immune responses are critical in SARS-CoV-2 virus infection. The goal of the study is to characterize changes of immune responses in different stages of SARS-CoV-2 infection and correlation with inflammatory cytokine production. The study will also identify key molecules in serum/plasma associated with cytokine storm. This study will provide essential information for precision treatment and determine strategies for vaccine development.

FinnGen recall study

Mari Niemi, FIMM

FinnGen utilises the genome data generated from biobank samples and health-related data from social and healthcare registers. However, not all information that is relevant to health research is available from national registers. For this reason, FinnGen now invites 6000 participants (Tampere: N=2000) to take part in new research sections. In these research sections, issues related to the different aspects of life are examined in more detail. These include a health and well-being survey and a collection of functional tests. Both sections can be filled in online via MyBiobank (OmaBiopankki) service. Using the new information gathered in these research sections, FinnGen researchers aim to understand what lifestyle factors, personal features and preferences together with genetic factors affect risk of becoming ill and the progression of possible diseases.

The FinnGen study already contains the genomic and health information of each invited person, and they have authorised their biobank to contact them in their Biobank Consent. FinnGen researchers do not know the identities or contact details of the invitees and that is why the invitations are sent by the biobanks. Finnish Clinical Biobank Tampere is a first hospital biobank to recontact participants electronically, via OmaTays portal.

Sirkku: Nanopartikkeleita ja proteiinien glykosylaatiota hyödyntävä määritysteknologia syöpien varhaiseen diagnostiikkaan

Katri Kuningas (Kaivogen Oy)

The purpose of the Sirkku-project is to develop and improve early cancer diagnostics. Project is based on the use of particle-based labels and new cancer specific biological binders. The aim is to develop new life saving diagnostic assays, which can help to decrease considerably the mortality rate of the cancer patients.

KIDLIB0 - Paikallisen munuaissyövän nestebiopsiatutkimus

Jussi Nikkola (Tays)

In this biobank and registry study we evaluate circulating tumor DNA from blood samples from patients who have undergone surgery for renal cell carcinoma. We study if preoperatively taken ctDNA can be used to predict disease recurrence in renal cell carcinoma.

PNET - Haiman neuroendokriinisten kasvainten merkkiainetutkimus

Hanna Seppänen (HUS), Johanna Laukkarinen (Tays)

Noin 1-2% kaikista haiman kasvaimista on neuroendokriinisia kasvaimia. Kasvaimet jaotellaan ns. toimiviin ja toimimattomiin kasvaimiin. On ajateltu, että pienimpien kasvainten osalta voidaan poistaa vain kasvain tekemättä suurempaa ja riskialttiimpaa haimaresektiota. Kuitenkin myös osa näistä varsin pienistä ja hyväennusteisena pidetyistä kasvaimista osoittautuu yllättäen haiman ulkopuolisiin imusolmukkeisiin levinneiksi. Näitä tapauksia on haasteellista tunnistaa nykyisellä diagnostiikalla. Tavoitteena on löytää uusia ennusteellisia tekijöitä haiman neuroendokriinisten kasvainten diagnostiikkaa ja hoidon suunnittelua varten. Analysoimme leikattujen potilaiden kudosnäytteistä paneelin immunohistokemiallisia immunohistokemiallisia markkereita TMA-tekniikalla , glykomiikkaa ja näiden assosiaation WHO-gradeeraukseen, kasvaimen stageen ja survivaliin sekä eri ennusteellisiin kuvantamislöydöksiin.

Retroperitoneoskooppisen lisämunuaiskirurgian tulokset TAYS:ssa 2010-2018

Päivi Pappinen ja Saara Metso (Tays)

Tutkimuksessa kuvataan Suomessa vielä vähän käytössä olevan selän kautta tähystyksellisesti tehtävän lisämunuaiskirurgian tulokset vuosina 2010-2018 ja leikkauksen oppimiskäyrä. Selvitämme, mitkä ennen leikkausta tehdyt radiologiset ja histologiset tekijät ennustavat lisämunuaiskasvaimen muuttumista pahanlaatuiseksi, uusiutumista ja leviämistä. Selvitämme myös leikattujen potilaiden pitkäaikaisennustetta, kuolleisuutta ja työkykyisyyttä. Tutkimuksesta saadaan kliinisesti merkittävää tietoa, jota voidaan hyödyntää lisämunuaiskasvainten diagnostiikassa, seurannassa ja hoidonsuunnittelussa sekä potilaiden informoinnissa.

The Ischemic Heart Disease Epitranscriptomics and Biomarkers Study (IHD-EPITRAN)

Antti Vento, Esko Kankuri, Vilbert Sikorski (HUS, HY)

On average, every fourth second ischemic heart disease (IHD) leads to death. Thus, IHD is the leading cause of death worldwide. IHD develops through deposition of lipids into the walls of coronary arteries. As a progressing disease, it narrows down the coronary arteries and limits blood flow to the heart causing an increasing amount of chest pains and dyspnea. Myocardial infarction, an acute life-threatening complication of IHD, underscores the dire need to detect IHD early on. In this way, effective preventive therapy measures could be initiated in time.

Modifications of genetic material (ribonucleic acids), epitranscriptomics, have recently been associated with IHD in experimental models.

This study collects blood samples from four distinct patient groups with or without IHD. Characterization of the epitranscriptomic modifications from the blood samples with new sequencing methods is expected to lead to discovery of novel biomarkers for future IHD diagnostics and drug development.

Nestebiopsioiden käyttö munuaissyövän diagnostiikassa, hoidossa ja seurannassa (KIDLIB1)

Jussi Nikkola (Tays)

We evaluate circulating tumor DNA from blood and urine samples from patients who have undergone surgery for renal cell carcinoma (RCC). We study if preoperatively taken ctDNA can be used to predict disease recurrence in renal cell carcinoma.

An individual mutation panel is established from patients' tumor tissue (fresh- or FFPE-sample) and serial blood and urine samples are collected during follow-up to study, if ctDNA might serve as a potential biomarker for predicting disease recurrence. We also include patients with metastatic RCC and study ctDNA as a biomarker for drug response and disease progression.

Tutkimus T-solulymfoomien patogeneesistä, differentiaalidiagnostiikasta, TWIST-proteiinin ekspression vaikutuksesta mycosis fungoideksen lääkeherkkyyteen sekä lymfomatoidin papuloosin ja ihon anaplastisen suurisoluisen T-solulymfooman eroista

Jenni Kiiskilä (Oulun yliopisto), Outi Kuittinen (Itä-Suomen yliopisto)

Lymfoomat ovat imukudoksen syöpiä. Ne ovat suuri ryhmä erilaisia pahanlaatuisia kasvaimia. Lymfomatoidi papuloosi (LyP) ja ihon primaarinen anaplastinen suurisoluinen T-solulymfooma (pcALCL) ovat histologialtaan samanlaisia tauteja, joista pcALCL on pahanlaatuinen ja LyP hyvänlaatuinen. Tautien erilaisen kliinisen käyttäytymisen vuoksi ne olisi tärkeää pystyä erottamaan toisistaan.

Angioimmunoblastinen T-solulymfooma (AITL) on harvinainen T-solulymfoomien tyyppi. Sen diagnosointi on alussa haastavaa, sillä alkuvaiheen tauti näyttää histologisesti benigniltä lymfoproliferaatiolta. Tässä tutkimuksessa haemme kliiniseen käyttöön soveltuvia keinoja, joiden tavoitteena on erottaa hyvänlaatuinen imusolmukkeiden suureneminen AITL:stä.

FinnGen EA3 study for data mining electronic health records for age-related macular degeneration (AMD) subtyping

Aarno Palotie (University of Helsinki)

Finngen EA3 combines gene data with clinical parameters and aims to understand better AMD etiology, progression, heterogeneity and who benefits most from existing treatments.

Nestebiopsioiden käyttö virtsatiesyövän diagnostiikassa, seurannassa ja hoidossa (UCLIB1)

Jussi Nikkola (Tays)

We evaluate circulating tumor DNA from blood and urine samples from patients who have undergone surgery for urothelial tumor (bladder or upper tract urothelial tumor). We study if preoperatively taken ctDNA can be used to predict disease recurrence in urothelial cancer.

An individual mutation panel is established from patients' tumor tissue (fresh- or FFPE-sample) and serial blood and urine samples are collected during follow-up to study, if ctDNA might serve as a potential biomarker for predicting disease recurrence. We also include patients with metastatic urothelial cancer and study ctDNA as a biomarker for drug response and disease progression.

Investigation of Disease-Associated T-cell Signatures in Autoimmune/Inflammatory Disorders

Adaptive Biotechnologies

The adaptive immune system is constantly responding to stimuli; from new and chronic infections to developing autoimmune diseases and cancer. The cells of the adaptive immune system display specialized receptors, T- and B-cell receptors (TCRs and BCRs), each with unique sequences in their genome encoding their receptor. It is estimated that every individual has on the order of 100 million unique receptors in their immunome, the collection of an individuals’ receptors, making it orders of magnitude larger than the genome. The massive diversity of the immunome has the potential to recognize millions of possible disease antigens, the ability to read the responses to these antigens will enable new diagnostics, therapies and understanding of diseases.

Adaptive Biotechnologies has developed a platform for sequencing the DNA of these receptors quantitatively and at high-throughput. In partnership with Microsoft, Adaptive has developed computational methods to identify TCR signatures for individual diseases by comparing TCR repertoires from cohorts of cases and controls. The aim of this project in partnership with FINBB is to identify TCR signatures across autoimmune and inflammatory diseases to enable new diagnostics and treatments.

Urologiset syövät Lynchin syndroomaa sairastavilla potilailla

Jukka-Pekka Mecklin (KSSHP)

Lynch syndrome (LS) is an autosomal inherited cancer syndrome that predisposes to almost all cancers in the abdominal area. Increased cancer susceptibility in syndrome is due to germline mutation in one or more DNA mismatch repair genes (MLH1, MSH2, MSH6, and PMS2). Urological cancers are the third most common type of cancer in LS patients after colorectal and endometrial cancers. As many as one-third of LS men develop prostate cancer and one-fifth of develop urothelial cancer. The risk of upper tract urothelial cancer is more than 10 times higher than in the general population.

Our aim is to study the clinico-pathological features and genetic background of urological cancers in LS patients in the Finnish LS registry. Molecular genetic profiles of tumors are analyzed and diagnostic markers are sought utilizing gene libraries. The results will be used in the organization of screening protocols for LS patients and in the development of tools for early diagnosis of urological cancers.

Lasten keliakia, potentiaalikeliakia ja diabetes Tampereen yliopistollisessa sairaalassa

Kalle Kurppa, Tays

Keliakia on yksi yleisimmistä ruuansulatuskanavan sairauksista. Taudin tunnistaminen on haastavaa moninaisen taudinkuvan vuoksi, ja suurin osa potilaista on diagnosoimatta. Tilannetta voitaisiin parantaa riskiryhmäseulonnalla, mutta tämän lähestymistavan paradoksaalinen seuraus on kasvava joukko keliakiavasta-ainepositiivisia potilaita, joilla on normaali suolinukkarakenne. Näille potilaille ei voida asettaa diagnoosia, vaikka he saattaisivat hyötyä taudin ruokavaliohoidosta.

Tampereella on kehitetty ns. mikro-CT kuvaus, joka saattaa paljastaa diagnostisen ohutsuolivaurion aiempaa herkemmin. Menetelmä mahdollistaa jopa koepalan pinta-alan mittauksen, jolloin se soveltuu myös aiempaa tarkempaan hoitovasteen seurantaan esim. lääketutkimuksissa. Tavoitteena on selvittää biopankkinäytteiden avulla potentiaalikeliaakikoiden ohutsuolikoepalojen mikro-CT-löydöksiä sekä kuvauksen toimivuutta kliinisessä diagnostiikassa. Lisäksi tutkitaan alkavaan keliakian liittyviä biologisia mekanismeja.