Genomic Medicine Sweden (GMS) has developed a broad gene panel for solid tumours that facilitates detailed diagnostics for current and next generation targeted therapies. The new gene panel will be implemented in routine healthcare during the autumn.

As precision medicine and targeted therapies have entered standard oncology care for several types of cancer, the need for a more specific molecular understanding of each individual tumor has become increasingly important for treatment decisions.

GMS’ working group for solid tumours has developed a broad gene panel that generates detailed molecular information from 560 genes linked to cancer. The panel has been validated in a national collaboration and will be implemented in routine healthcare via Sweden’s seven university hospitals during autumn 2022.

Flexible gene panel

Anders Edsjö. Photo: Nooreldin Zendehrokh.

“There are many reasons why we chose to develop our own gene panel. By keeping the design and development in-house, we can promptly add diagnostic functions as future clinical needs arise. One such example is the complex biomarker HRD,” explains Anders Edsjö, co-chair of GMS Solid Tumours and senior consultant at the Department of clinical genetics, pathology and molecular diagnostics at Region Skåne.

Homologous recombination deficiency (HRD) is included in the panel in order to predict responses to the treatment of ovarian cancer with PARP inhibitors but is also expected to prove valuable for tumor subtyping and treatment decisions in other types of cancer in the future.

Johan Botling. Photo: private.

“Our approach has been to cover treatment predictive molecular target changes within the framework of precision oncology as well as diagnostic needs for genetic subtyping of tumours within diagnostic molecular pathology,” says Johan Botling, co-chair of GMS Solid Tumours, senior consultant at Uppsala University Hospital.

The panel also includes genes which are not currently associated with a treatment choice but which are nonetheless known to have an impact on the growth and behaviour of cancer tumors. This will provide patients with new opportunities to join clinical trials and qualify for new targeted therapies.

Interprofessional collaboration

“To solve the inherent complexity in developing such a broad panel, we have gathered an interprofessional team of pathologists, molecular biologists, bioinformaticians and other professions,” says Johan Botling.

The work to develop the GMS560 panel has involved over a hundred experts from all seven regional Genomic Medicine Centers (GMCs) at Sweden’s university hospitals as well as affiliated regional laboratories and the SciLifeLab Clinical Genomics platform.

Genomic Medicine Sweden’s organisation as a nation-wide collaboration has made it possible to assemble the necessary resources to develop technical solutions for all diagnostic issues addressed by the GMS560 platform. The validation of so called mutational signatures was divided between various GMC/Clinical Genomics nodes: GMC/Clinical Genomics Uppsala was focused on tumour mutational burden (TMB), GMC/Clinical Genomics Lund on homologous recombination deficiency (HRD) and GMC/Clinical Genomics Örebro on microsatellite instability (MSI).

Implementation in healthcare

Having undergone extensive validation over the past year, the GMS560 panel is now ready for implementation in the healthcare system. Each regional healthcare provider will put the GMS560 platform into operational use, determined to a large extent by recommendations in the national treatment guidelines for each cancer in hand.

“If all goes as planned, the new comprehensive gene panel will be a vital cornerstone of future cancer care – facilitating safer diagnostics, prognostics and treatment predictions,” says Anders Edsjö.

Figure. The GMS560 gene panel includes single nucleotide variants (SNVs), copy number variants (CNVs), insertion-deletion mutations (InDels), structural variants, gene fusions, homologous recombination deficiency (HRD), microsatellite instability (MSI) and tumour mutational burden (TMB).

Illustration: Lucia Cavelier
Photo: iStock photos