Abstract
Comprehensive genomic profiling (CGP) is gradually becoming an inevitable part of the everyday oncology clinical practice. The interpretation and optimal implementation of the results is one of the hot topics of modern-day oncology. According to the recent findings, uterine cancer harbors a high level of gene alterations but is still insufficiently explored. The primary goal of this project was to assess the proportion of patients with targetable mutations. Also, the aim was to define and emphasize potential opportunities as well as the problems we have faced in the first year of testing on the national level. We performed a multicentric, retrospective, nested cross-sectional analysis on the total population of Croatian patients with advanced/metastatic uterine cancer where the tumor CGP was performed during 2020. CGP of the tumor tissue of 32 patients revealed clinically relevant genomic alterations (CRGA) in 27 patients (84%) with a median of 3 (IQR 1-4) CRGA per patient. The most common CRGAs were those of phosphatide-inositol-3 kinases (PIK3) in 22 patients (69%), with 13/22 (59%) of those patients harboring PIK3CA mutation. The next most common CGRAs were ARID1A and PTEN mutations in 13 (41%) and 11 (34%) patients, respectively. Microsatellite status was determined as stable in 21 patients (66%) and highly unstable in 10 patients (31%). A high tumor mutational burden (≥10Muts/Mb) was reported in 12 patients (38%). CGP analysis reported some kind of targeted therapy for 28 patients (88%). CGP determined clinically relevant genomic alterations in the significant majority of patients with metastatic uterine cancer, defining it as a rich ground for further positioning and development of precision oncology.
Highlights
Revolutionary advancement of diagnostics through the optimal implementation of informational technologies and development of bioinformatics, combined with a better understanding of the human genome and discovery of the comprehensive genomic testing, has led towards a more individualized and targeted approach to the patient, making the first half of the 21st century a paradigm shift in the establishment of postulates of precision medicine
According to the TCGA (The Cancer Genome Atlas) project in 2013, uterine cancer/endometrial cancer is divided into four subgroups based on the genomic profiling of 373 endometrial cancer specimens [POLE ultra-mutated, microsatellite instability group, copy number low (CNL), and copy number high (CNH) groups][19]
The microsatellite status was based on genomewide analysis of 95 microsatellite loci, while tumor mutational burden (TMB) was determined by counting all synonymous and non-synonymous variants present at 5% allele frequency or greater, and the total number was presented as mutations per megabase (Muts/Mb) unit [22, 23, 24]
Summary
Revolutionary advancement of diagnostics through the optimal implementation of informational technologies and development of bioinformatics, combined with a better understanding of the human genome and discovery of the comprehensive genomic testing, has led towards a more individualized and targeted approach to the patient, making the first half of the 21st century a paradigm shift in the establishment of postulates of precision medicine. Definition of underlying causes of carcinogenesis and progress in the field of molecular biology has enabled the development of novel treatment approaches such as moleculartargeted therapy and immunotherapy with improved outcomes and impact on patients survival. According to the TCGA (The Cancer Genome Atlas) project in 2013, uterine cancer/endometrial cancer is divided into four subgroups based on the genomic profiling of 373 endometrial cancer specimens [POLE ultra-mutated, microsatellite instability group, copy number low (CNL), and copy number high (CNH) groups][19]. At the end of 2019, comprehensive genomic profiling (CGP) provided by Foundation Medicine Inc. (FMI) became free in Croatia [20]
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