Maria has suffered from stomach aches and intensive skin itching for over a week before she contacted a physician. She was admitted to the local gastroenterological clinic and after being subjected series of medical tests she was confronted with a grim diagnosis: pancreatic cancer.
Being a medical professional herself, she was aware how difficult it is to treat pancreatic cancer. Therefore, she insisted on best possible diagnostic option – comprehensive analysis of a cancer genome. She was hoping to find genetic changes, that could offer better therapeutical options than these available as a standard of care. A member of her family heard about genomic profiling performed at MNM Diagnostics and she immediately decided to order the full profiling of her cancer genome.

MNM Diagnostics Onco Team performed a comparison between her healthy genome (from DNA isolated from blood) with her cancer genome isolated from tumour material. Thorough analysis of her healthy genome demonstrated that there is no single mutation predisposing her to develop cancer. On the other hand, the complexity of her cancer was striking. The tumour was described as genetically stable even though there were more than 3000 mutations present in cancer cells. Two particular genetic variants were found as cancer drivers: TP53 and CDKN2A. Pathogenic mutations in these genes lead to uncontrolled cell divisions and spreading. Understanding is a key in fighting cancer, knowing cancer drivers allows for effective treatment selection. Mutated CDKN2A is a target for a novel class of drugs, cyclibs, which are available in clinical practice.

Further analysis revealed other features of her cancer: there was no Microsatellite Instability (MSI=0%) and the Total Mutation Burden was low (TMB<1/Mbp), so she would not benefit much from PD-1/PD-L1 immunotherapy. Unfortunately, the other therapeutic option- the PARP inhibitors, would not have been suitable for her either, because she didn’t have homologous recombination deficiency. However, detailed analysis of structural variant in her tumour genome showed amplification of a gene PIM1 (kinase promoting cell cycle progression), resulting in accelerating cell cycle. There is a therapy targeted for the JAK-STAT pathway, involving PIM1 being tested for pancreatic cancer and it is already registered for treatment of different malignancies.

At the moment Maria’s disease is stable, even though she suffered from polychemotherapy side effects. Her cancer is under control since targeted therapies just work.

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