Technology leadership in the early detection of gynecological tumors

Sola Diagnostics GmbH

Sola Diagnostics GmbH, based in Innsbruck, was founded in 2020 by Prof. Martin Widschwendter.

The Company aims to develop academic inventions from his research groups in London, Stockholm and Innsbruck into technologies that help women worldwide detect gynecological tumors at an early stage.

Our licensees are diagnostic laboratories that ensure these innovative technologies for the prevention of gynecological tumors are made available to patients in the fastest possible way.

Principal shareholders of Sola Diagnostics

Besides Prof Widschwendter, The Eve Appeal and the University of Innsbruck are major shareholders of Sola Diagnostics GmbH.

The Eve Appeal is the UK’s leading charity supporting research and education on the five gynecological cancers of the uterus, cervix, ovary, vulva and vagina.

Prof Dr Martin Widschwendter

Professor Dr Martin Widschwendter

Prof Dr Martin Widschwendter is a gynecologic oncologist and pioneer in the field of primary and secondary prevention of gynecologic cancer using epigenetic DNA methylation makers.

He is head of the EUTOPS Institute at the University of Innsbruck, a professor at University College London and holds a visiting professorship at the Karolinska Institute in Stockholm.

Scientific milestones of Prof Widschwendter

1997 - Epigenetic Field Cancerization

We demonstrated that normal breast tissue adjacent to a breast cancer contained molecular changes that may predispose the breast to form a cancer. We showed that the changes were triggered by abnormal DNA methylation. This has become known as epigenetic field cancerization.

Widschwendter M, Berger J, Daxenbichler G, Müller-Holzner E, Widschwendter A, Mayr A, Marth C, Zeimet AG. Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer. Cancer Res. (1997); 57:4158-4161. PMID: 9331065.

Widschwendter M, Berger J, Hermann M, Müller HM, Amberger A, Zeschnigk M, Widschwendter A, Abendstein B, Zeimet AG, Daxenbichler G, Marth C. Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer. J Natl Cancer Inst. (2000); 92:826-832. PMID: 10814678.

2004 - Epigenetics in Surrogate Tissue (cfDNA)

Cancer detection typically requires direct access to the tumor via (often very invasive) sampling methods. We were one of the first who assessed the analysis of cell-free DNAme in serum/plasma for cancer detection and assessment of minimal residual disease and outcome (examples provided are for breast and cervical cancer).

Müller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E, Marth C, Widschwendter M. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. (2003); 63:7641-7645. PMID: 14633683.

Widschwendter A, Ivarsson L, Blassnig A, Müller HM, Fiegl H, Wiedemair A, Müller-Holzner E, Goebel G, Marth C, Widschwendter M. CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients. Int J Cancer. (2004); 109:163-166. PMID: 14750164

2004 - Epigenetics for Colorectal Cancer (i.e. fecal sample)

We were the first to assess whether DNA methylation in stool samples is able to detect colorectal cancer.

Müller HM, Oberwalder M, Fiegl H, Morandell M, Goebel G, Zitt M, Mühlthaler M, Ofner D, Margreiter R, Widschwendter M. Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet. (2004); 363:1283-1285. PMID: 15094274.

2004 - Epigenetics in Self-Sampled Cervico-Vaginal Fluid

Our early studies showed the potential of samples of fluid from the vagina for early cancer detection. We showed that DNA methylation of a few regions in a sample of vaginal fluid collected on a tampon is able to identify women with endometrial or cervical cancer.

Fiegl H, Gattringer C, Widschwendter A, Schneitter A, Ramoni A, Sarlay D, Gaugg I, Goebel G, Müller HM, Mueller-Holzner E, Marth C, Widschwendter M. Methylated DNA collected by tampons–a new tool to detect endometrial cancer. Cancer Epidemiol Biomarkers Prev. (2004); 13:882-888. PMID: 15159323.

Widschwendter A, Gattringer C, Ivarsson L, Fiegl H, Schneitter A, Ramoni A, Müller HM, Wiedemair A, Jerabek S, Müller-Holzner E, Goebel G, Marth C, Widschwendter M. Analysis of aberrant DNA methylation and human papillomavirus DNA in cervicovaginal specimens to detect invasive cervical cancer and its precursors. Clin Cancer Res. (2004); 10:3396-3400. PMID: 15161694.

2007 - PCGT-Methylation Cellular Aging and Cancer

We pioneered the concept that aberrant DNA methylation at gene promoter sites, which are (reversibly) occupied by the Polycomb Repressor Complex 2 in stem cells, are heavily methylated in cancer. This paper was the first to support the concept that blocking the differentiation of stem cells due to epigenetic mechanisms is one of the key contributing factors to cancer formation. Describe the concept that these Polycomb Group Target Genes (PCGTs) lock stem cells in an undifferentiated status and thereby predispose these cells to cancer transformation. Our later and ongoing studies demonstrate that methylation of these PCGT regions is triggered by age, cell replication and by various exposures like smoking.

Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger DJ, Campan M, Young J, Jacobs I, Laird PW. Epigenetic stem cell signature in cancer. Nat Genet. (2007); 39:157-158. PMID: 17200673.

2009 - EWAS - Epigenome Wide Association Studies

We performed the first larger-scale epigenotyping study, demonstrating that DNA methylation may serve as a link between the environment and the genome. Modifiable factors, like hormones, leave an imprint in the DNA of cells that are unrelated to the target organ and indicate the predisposition of an individual to develop cancer.

Widschwendter M, Apostolidou S, Raum E, Rothenbacher D, Fiegl H, Menon U, Stegmaier C, Jacobs IJ, Brenner H. Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS One (2008 Jul 16); 3(7):e2656. PMID: 18628976.

2008 - Tissue Specificity of the Epigenome

This research highlighted the importance of considering the cell-type specificity of the epigenome when utilizing it for disease prediction. We developed a DNAme based risk predictor for ovarian cancer by comparing blood DNA from women with and without active ovarian cancer with a Receiver Operator Characteristic Area Under the Curve significantly in excess of 0.8 in an independent validation set. However, we eventually realized that the actual DNAme profile was a reflection of the increased granulocyte/lymphocyte ratio which was elevated in women with active ovarian cancers and not an indicator of future risk.

Teschendorff AE. Menon U, Gentry-Maharaj A, Ramus SJ, Gayther SA, Apostolidou S, Jones A, Lechner M, Beck S, Jacobs IJ & Widschwendter M. An epigenetic signature in peripheral blood predicts active ovarian cancer. PLoS One. (2009 dec); 4(12), e8274. PMID: 20019873.

2018 - Cancer Risk Prediction in Surrogate Tissue

We were the first to demonstrate that epigenetic footprints in hormone-sensitive cervical cells are a good proxy that best captures the risk for various women-specific cancers, including breast cancer.

Barrett JE, Herzog C, Jones A, Leavy OC, Evans I, Knapp S, Reisel D, Nazarenko T, Kim Y-N, Franchi D, Ryan A, Franks J, Bjørge L, Zikan M, Cibula D, Harbeck N, Colombo N, Dudbridge F, Jones L, Sundström K, Dillner J, Flöter Rådestad A, Gemzell-Danielsson K, Pashayan N, Widschwendter M. The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples. Nat Commun. (2022 Feb 01); 13(1):449. doi: 10.1038/s41467-021-27918-w. PMID: 35105882.

2022 - Epigenetics Monitoring for Primary Prevention of Breast Cancer

We describe the potential for individualized breast cancer prevention and risk monitoring using antiprogestins and a novel type of epigenetic test, the WID-Breast29. Our findings may be particularly valuable for individuals at the highest risk, for instance, BRCA mutation carriers.

Bartlett TE, Evans I, Jones A, Barrett JE, Haran S, Reisel D, … Howell SJ, Risques RA, Flöter Rådestad A, Dubeau L, Gemzell-Danielsson K, Widschwendter M. Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women. Genome Med. (2022 Jun 15); 14(1):64. doi: 10.1186/s13073-022-01063-5. PMID: 35701800