The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determ…

502P Impact of different selection approaches for identifying Lynch syndrome-related colorectal cancer patients

POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes

POLE, POLD1, and NTHL1 are involved in DNA replication and have recently been recognized as hereditary cancer-predisposing genes, because their alterations are associated with colorectal cancer and other tumors. POLE/POLD1-associated syndrome shows an autosomal dominant inheritance, whereas NTHL1-associated syndrome follows an autosomal recessive pattern. Although the prevalence of germline monoallelic POLE/POLD1 and biallelic NTHL1 pathogenic variants is low, they determine different phenotypes with a broad tumor spectrum overlapping that of other hereditary conditions like Lynch Syndrome or Familial Adenomatous Polyposis. Endometrial and breast cancers, and probably ovarian and brain tumo…

1535P Exploring the dynamic crosstalk between immune system and genetics in a cohort of 116 completely resected gastrointestinal stromal tumors (GISTs)

162P Prevalence and spectrum analysis of germline BRCA1 and BRCA2 variants of unclear significance in HBOC Syndrome: Decoding the mysterious signals of the genome

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relativ…

166P Hereditary breast, ovarian and pancreatic cancers: Looking beyond the BRCA1/2 genes

Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2

Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…

247P Population-based testing for hereditary breast and ovarian cancer in a cohort of 1,346 patients from Southern Italy (Sicily): When historical background affects genetics

Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/2 genes

Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlini…

738P Soluble PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTN2A1 as predictive biomarkers of nivolumab response in patients with metastatic clear cell renal carcinoma

BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients wit…

167P Role of the multi-gene panel testing for detection of pathogenic variants in patients with hereditary bilateral breast cancer

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlini…