Italian 
English Profilo molecolare multigenico somatico di pazienti affette da cancro ovarico sieroso ad alto grado a lunga sopravvivenza e BRCA-negative
Molecular profile of BRCA-negative long survivor High Grade Serous Ovarian Cancer patients using a somatic multigene panel
AUTORI
1Laboratorio di Diagnostica Molecolare e Genomica, Unità Operativa Complessa di Chimica, Biochimica e Biologia Molecolare, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma
2Divisione di Ginecologia Oncologica, Dipartimento di Ostetricia e Ginecologia, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Roma
ABSTRACT
Molecular profile of BRCA-negative long survivor High Grade Serous Ovarian Cancer patients using a somatic multigene panel
Introduction: High Grade Serous Ovarian Cancer (HGSOC) is the most common subtype of ovarian cancer. Approximately half of HGSOCs are characterized by inactivation of Homologous Recombination (HR) genes, such as BRCA1/2. Given the practical certainty of recurrence in relapsed HGSOC after platinum-based chemotherapy, a maintenance approach with Poly-ADP Ribose Polymerase inhibitors (PARPi) has improved progression-free survival in BRCA1/2 mutated patients. Besides BRCA1/2 defects, there are no predictive biomarkers for sensitivity to platinum-based chemotherapy and PARPi. Molecular studies of BRCA-negative long survivor patients could be of help in identifying additional biomarkers of prolonged response.
Methods: a total of 20 fresh frozen tumor samples obtained from long survivor BRCA-negative HGSOC patients were investigated using a Next Generation Sequencing (NGS) multigene panel. Nucleotide variants and copy number variations of ATM, BARD1, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD51C, RAD51D, STK11 and TP53 genes were tested.
Results: in this cohort 17 mutated subjects (17/20; 85%) with 15 pathogenic/variants of unknown clinical significance (VUS) in TP53 have been found; nucleotide variants have been identified also in ATM (n=1), PALB2 (n=1), BRIP1 (n=2), BARD1 (n=1) and NBN (n=1).
Discussion: the durable response to therapy observed in our patients may be multifactorial and partially driven by germline/somatic mutations in HR genes. An extended investigation is mandatory to obtain a more comprehensive overview on the genetic status of this selected cohort of patients. Querying genes other than BRCA1/2 would be of an extremely important benefit, allowing the clinicians to evaluate the correlation between molecular and clinical features and to acquire more appropriate genetic information useful in the eligibility to target therapy.