Onkológia 3/2022

Recent applications of massive parallel sequencing in cancer diagnosis and treatment

Introduction: Personalized management plays a key role in ensuring appropriate prophylaxis, prevention as well as personalized treatment for cancer patients. Hereditary cancer syndromes underlie approximately 5 to 10% of all cancers, i.e. one or more genes may be responsible for a serious genetic predisposition. Massive parallel sequencing technologies are currently used to detect causal variants, allowing thousands of genes and hundreds of patients to be analyzed at once. Massive parallel sequencing methods are also currently used to determine the genomic profile of the tumor, based on which it is possible to identify subgroups of patients benefiting from systemic therapy, minimize the negative impact of side effects, determine the prognosis of the disease and better classify tumor subtypes. Material and methods: Two approaches were used to test families with inherited cancers: a panel analysis of 38 genes (Custom Hereditary Cancer Solution, SOPHiA Genetics) and a clinical exoma analysis involving 4571 genes (Clinical Exome Solution, SOPHiA Genetics). Three approaches were used to analyze the genomic profile of the tumor: Panel analysis of 523 genes (TruSight Oncology 500, Illumina), panel analysis (Solid Tumor Solution +, SOPHiA Genetics) and analysis of gene fusion panel (RNAtarget Oncology Solution, SOPHiA Genetics). All analyzes were performed on Illumina platforms (Miseq and Nextseq 550) and bioinformatics analysis was performed using SOPHiA DDM® and Illumina PierianDX software. Results and conclusion: Altogether 3878 families with inherited cancers were examined at the Department of Medical Genetics of St. Elizabeth Cancer Institute, where pathogenic or probably pathogenic variants were identified in 716 cases (approximately 20%). The most common causal variants were detected in the genes BRCA1, BRCA2, CHEK2, ATM, PALB2, NBN, MUTYH, BARD1, BLM, BRP1, MSH6, POLE. The genomic profile of the tumor was determined in 207 patients. Of the total number of variants detected, 37.5% of the variants had strong clinical significance (TIER class I) and 62.5% of variants had potential clinical significance (TIER class II). The most frequently mutated gene was the TP53 gene, in which mutations accounted for 33.3% of all clinically significant variants. The application of massive parallel sequencing enables early diagnosis of hereditary and sporadic cancer, minimizes treatment costs by shifting the current traditional medical approach to the treatment of oncological diseases to an individual and predictive approach.

Keywords: MPS, gene panel, clinical exome, CGP, personalized medicine