Johan Botling's research projects in molecular tumour pathology

The molecular pathology of non-small cell lung cancer

Knowledge of the landscape of driving mutations in unselected real-life patient populations is crucial for the implementation of modern precision oncology. We have characterised genetic aberrations in tumour samples from a regional population-based lung cancer cohort. Molecular data in combination with clinical follow-up and cancer registry parameters form the base for diagnostic and predictive biomarker research.

Using fresh frozen tissues from surgical specimens we have characterised novel prognostic copy number (Micke et al. 2011) and gene expression biomarkers (Botling et al., 2013). Currently, we study somatic mutation patterns based on deep sequencing, and complex mutation combinations are further explored by novel in situ techniques (Grundberg et al., 2014). In a novel collaboration we aim to clarify the role and compartment specific regulation of tumour-associated macrophages with regard to immunosuppressive features.

Full population-based comprehensive diagnostic coverage (Sandelin et al., 2015) forms the basis for fair and equal cancer care and provides a foundation for inclusion of patients with specific alterations into clinical and translational research. In the U-CAN project, with focus on advanced disease, we strive to implement comprehensive biobanking of tissues and liquid biopsies in connection to structured clinical data. This effort is now extended to regional community hospitals in parallel to launch of novel multiplex diagnostics of treatment targets by targeted NGS and RNA-based methods.

International collaborations have resulted in a number of publications over the last years, including the landmark genomic characterization of small cell lung cancer conducted by a consortium led by the Cologne translational oncology group (George et al., 2015).
 

Translation to diagnostic molecular pathology

A key priority of our group is to translate knowledge and established technology developed in research projects into routine pathology diagnostics. To this end, somatic mutation assays for cancer specimens (KRAS, NRAS, BRAF, EGFR and PIK3CA) have been implemented at the molecular pathology unit at the hospital Department of Pathology. Our group leads the Solid Tumor Work Package (WP.1) in the national Clinical Genomics platform (Science for Life Laboratory).

The development of targeted NGS and linked bioinformatic pipelines adapted to formalin-fixed paraffin-embedded cancer biopsies (Moens et al., 2015) has led to the launch of multiplex diagnostic mutation assays for colon cancer (2014), lung cancer (2015), melanoma and GIST (2016) in routine health care. This year targeted sequencing diagnostics was launched for circulating tumour DNA in liquid biopsies.

Ongoing work includes RNA-assays for fusion gene detection and global tumour profiling in prospective clinical trials. Our goal is to push and translate explorative research into cutting edge cancer diagnostics for patients through close clinical research collaborations.
 

Cooperating groups:
Arne Östman, Cancer Center Karolinska
Fredrik Pontén, Uppsala University

Links:
American Association of Molecular Pathology
International Association for the Study of Lung Cancer
Swedish Society of Pathology
International Academy of Pathology