Romanian Society of Pharmaceutical Sciences
 

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IDENTIFICATION OF PHARMACOLOGICALLY RELEVANT MUTATIONS IN ENDOMETRIAL CANCER BY WHOLE-EXOME SEQUENCING OF FFPE TUMOUR SAMPLES

ROBERT BOTEA 1,2, MADALINA PIRON-DUMITRASCU 1,2, TIBERIU AUGUSTIN GEORGESCU 3,4, SILVIU CRISTIAN VOINEA 5,6*, VALENTIN NICOLAE VARLAS 1,7, SIMONA RALUCA IACOBAN 1*, NICOLAE SUCIU 1,2

1 Department of Obstetrics and Gynaecology, “Carol Davila” University of Medicine and Pharmacy, 38-52 Gh. Polizu Street, 011062, Bucharest, Romania
2 Department of Obstetrics and Gynaecology, “Alessandrescu-Rusescu” National Institute of Mother and Child Health, 38-52 Gh. Polizu Street, 011062, Bucharest, Romania
3 Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, 38-52 Gh. Polizu Street, 011062, Bucharest, Romania
4 Department of Pathology, “Alessandrescu-Rusescu” National Institute of Mother and Child Health, 38-52 Gh. Polizu Street, 011062, Bucharest, Romania
5 Department of Oncological Surgery, “Carol Davila” University of Medicine and Pharmacy, 252 Fundeni Road, 022328, Bucharest, Romania
6 Department of Oncological Surgery, “Alexandru Trestioreanu” Oncology Institute, 252 Fundeni Road, 022328, Bucharest, Romania
7 Department of Obstetrics and Gynaecology, “Filantropia” Obstetrics and Gynaecology Clinical Hospital, 11-13 Ion Mihalache Boulevard., 011132, Bucharest, Romania

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Endometrial cancer is a prevalent gynaecologic cancer, but it is far from being homogeneous. It shows an exceptionally diverse genetic background and requires highly personalised treatment plans. In this study, we performed whole-exome sequencing (WES) on formalin-fixed, paraffin-embedded (FFPE) tumour samples from 13 patients with histologically confirmed endometrial cancer in order to identify pharmacologically relevant mutations. This study focused on oncogenic and tumour suppressor gene mutations that novel therapies might target. Variants in the PIK3CA, PTEN, KRAS, ARID1A, TP53 and mismatch repair genes (MLH1 and MSH2) were interesting. We identified 352 unique variants, with significant mutations observed in PIK3CA (8 patients), PTEN (6 patients), KRAS (4 patients) and ARID1A (5 patients). The mutations were classified as either pathogenic or likely pathogenic. These could be potential targets for existing or experimental therapies. We have found several mutations, possibly actionable by drugs like PI3K inhibitors, mTOR inhibitors and immune checkpoint inhibitors. This research demonstrates the massive potential of WES to reveal the genetic background of endometrial cancer that could help clinicians refine and personalise the treatment options of these patients.