Spectrum of Germline Pathogenic Variants in BRCA1/2 Genes in the Apulian Southern Italy Population: Geographic Distribution and Evidence for Targeted Genetic Testing

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we re...

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Hauptverfasser: Patruno, Margherita, De Summa, Simona, Resta, Nicoletta, Caputo, Mariapia, Costanzo, Silvia, Digennaro, Maria, Pilato, Brunella, Bagnulo, Rosanna, Pantaleo, Antonino, Simone, Cristiano, Natalicchio, Maria Iole, De Matteis, Elisabetta, Tarantino, Paolo, Tommasi, Stefania, Paradiso, Angelo
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Veröffentlicht: Basel MDPI AG 21.09.2021
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Abstract BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.
AbstractList BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype-phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a "founder effect". Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype-phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a "founder effect". Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.
BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.
Simple SummaryBRCA1 and BRCA2 are two major high-penetrance breast/ovarian cancer predisposition genes, whose mutations can lead to high risk and early onset of breast and ovarian cancer. Numerous studies are focused on spectrum and prevalence of BRCA1/2 mutations worldwide. This is the first study that exclusively focused on native Apulian probands. We found that ten recurrent BRCA1/2 pathogenic variants account for more than half of the patients with proven HBOC syndrome from Apulia. Besides BRCA1 c.5266dupC, which is present in significant numbers in every Apulian province, the other PVs occur at a high frequency in some areas and not others. In-depth knowledge of the mutation spectrum of the target population and of the relatively small number of recurrent mutations is crucial to develop a specific cost-effective strategy for mutation screening and a program for breast–ovarian cancer control and prevention through more liberal, yet rational, genetic testing and counseling.AbstractBRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects.
Author Resta, Nicoletta
Caputo, Mariapia
Paradiso, Angelo
Pantaleo, Antonino
Natalicchio, Maria Iole
Tommasi, Stefania
Digennaro, Maria
Tarantino, Paolo
Bagnulo, Rosanna
Costanzo, Silvia
Patruno, Margherita
Pilato, Brunella
Simone, Cristiano
De Matteis, Elisabetta
De Summa, Simona
AuthorAffiliation 5 Section of Clinic Pathology, OO.RR., 71122 Foggia, Italy; iole.nat@tiscali.it
4 Medical Genetics, National Institute of Gastroenterology “S. de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy
3 Medical Genetics Unit, Department of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari, Policlinico Hospital Bari, 70124 Bari, Italy; nicoletta.resta@uniba.it (N.R.); rosanna.bagnulo@uniba.it (R.B.); antonino.pantaleo@uniba.it (A.P.); cristiano.simone@uniba.it (C.S.)
7 Medical Genetics Unit, “Vito Fazzi” Hospital, 73100 Lecce, Italy; bt.tarantino@gmail.com
2 Molecular and Pharmacogenetics Diagnostic Laboratory, IRCCS-IstitutoTumori “Giovanni Paolo II”, 70124 Bari, Italy; m.caputo@oncologico.bari.it (M.C.); b.pilato@oncologico.bari.it (B.P.); s.tommasi@oncologico.bari.it (S.T.)
1 Center for Hereditary Tumors Research, Istituto Tumori Bari, Giovani Paolo II, IRCCS, 70124 Bari, Italy; s.costanzo@oncologico.bari.it (S.C.); m.digennaro@oncologico.bari.it (M.D.); a.pa
AuthorAffiliation_xml – name: 4 Medical Genetics, National Institute of Gastroenterology “S. de Bellis” Research Hospital, Castellana Grotte, 70013 Bari, Italy
– name: 1 Center for Hereditary Tumors Research, Istituto Tumori Bari, Giovani Paolo II, IRCCS, 70124 Bari, Italy; s.costanzo@oncologico.bari.it (S.C.); m.digennaro@oncologico.bari.it (M.D.); a.paradiso@oncologico.bari.it (A.P.)
– name: 5 Section of Clinic Pathology, OO.RR., 71122 Foggia, Italy; iole.nat@tiscali.it
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– name: 6 Oncology Unit, “Vito Fazzi” Hospital, 73100 Lecce, Italy; dr.dematteis.elisabetta@gmail.com
– name: 7 Medical Genetics Unit, “Vito Fazzi” Hospital, 73100 Lecce, Italy; bt.tarantino@gmail.com
– name: 3 Medical Genetics Unit, Department of Biomedical Sciences and Human Oncology, “Aldo Moro” University of Bari, Policlinico Hospital Bari, 70124 Bari, Italy; nicoletta.resta@uniba.it (N.R.); rosanna.bagnulo@uniba.it (R.B.); antonino.pantaleo@uniba.it (A.P.); cristiano.simone@uniba.it (C.S.)
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CitedBy_id crossref_primary_10_1016_j_critrevonc_2022_103626
crossref_primary_10_3390_ijms252312640
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Snippet BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and...
Simple SummaryBRCA1 and BRCA2 are two major high-penetrance breast/ovarian cancer predisposition genes, whose mutations can lead to high risk and early onset...
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StartPage 4714
SubjectTerms Age
BRCA1 protein
BRCA2 protein
Breast cancer
Data collection
Founder effect
Genes
Genetic screening
Genotypes
Geographical distribution
Males
Mutation
Ovarian cancer
Patients
Phenotypes
Population
Population studies
Tumors
Title Spectrum of Germline Pathogenic Variants in BRCA1/2 Genes in the Apulian Southern Italy Population: Geographic Distribution and Evidence for Targeted Genetic Testing
URI https://www.proquest.com/docview/2576382979
https://www.proquest.com/docview/2577448458
https://pubmed.ncbi.nlm.nih.gov/PMC8467705
Volume 13
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