Whole‐exome sequencing and targeted gene sequencing provide insights into the role of <i>PALB2</i> as a male breast cancer susceptibility gene

Silvestri, Valentina; Zelli, Veronica; Valentini, Virginia; Rizzolo, Piera; Navazio, Anna Sara; Coppa, Anna; Agata, Simona; Oliani, Cristina; Barana, D.; Castrignanò, Tiziana; Viel, Alessandra; Russo, Antonio; Tibiletti, Maria Grazia; Zanna, Ines; Masala, Giovanna; Cortesi, Laura; Manoukian, Siranoush; Azzollini, Jacopo; Peissel, Bernard; Bonanni, Bernardo; Peterlongo, Paolo; Radice, Paolo; Palli, Domenico; Giannini, Giuseppe; Chillemi, Giovanni; Montagna, Marco; Ottini, Laura

doi:10.1002/cncr.30337

Cited by 33 publications

(22 citation statements)

References 45 publications

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“…Among non‐ BRCA1/2 genes a significant role of PALB2 in MBC susceptibility emerged. We have previously shown that PALB2 plays a relevant role in high‐risk, non‐ BRCA1/2 MBC cases . In the present study, more than 1% of non‐ BRCA1 / 2 MBC cases, unselected for FH of BC/OC had a germline PALB2 pathogenic variant.…”

Section: Discussionsupporting

confidence: 44%

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Rizzolo

Zelli

Silvestri

et al. 2019

Intl Journal of Cancer

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Breast cancer (BC) in men is rare and genetic predisposition is likely to play a relevant role in its etiology. Inherited mutations in BRCA1/2 account for about 13% of all cases and additional genes that may contribute to the missing heritability need to be investigated. In our study, a well‐characterized series of 523 male BC (MBC) patients from the Italian multicenter study on MBC, enriched for non‐BRCA1/2 MBC cases, was screened by a multigene custom panel of 50 cancer‐associated genes. The main clinical‐pathologic characteristics of MBC in pathogenic variant carriers and non‐carriers were also compared. BRCA1/2 pathogenic variants were detected in twenty patients, thus, a total of 503 non‐BRCA1/2 MBC patients were examined in our study. Twenty‐seven of the non‐BRCA1/2 MBC patients were carriers of germline pathogenic variants in other genes, including two APC p.Ile1307Lys variant carriers and one MUTYH biallelic variant carrier. PALB2 was the most frequently altered gene (1.2%) and PALB2 pathogenic variants were significantly associated with high risk of MBC. Non‐BRCA1/2 pathogenic variant carriers were more likely to have personal (p = 0.0005) and family (p = 0.007) history of cancer. Results of our study support a central role of PALB2 in MBC susceptibility and show a low impact of CHEK2 on MBC predisposition in the Italian population. Overall, our data indicate that a multigene testing approach may benefit from appropriately selected patients with implications for clinical management and counseling of MBC patients and their family members.

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Section: Discussionsupporting

confidence: 44%

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Rizzolo

Zelli

Silvestri

et al. 2019

Intl Journal of Cancer

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“…Two high-penetrance breast cancer genes, BRCA1 and BRCA2, are thought to be responsible for only 13% of MBC (71), and multiple genetic factors remain unknown. To date, many PVs of PALB2 have been reported in MBC patients (72)(73)(74)(75)(76). In 2017, Pritzlaff et al uncovered that PALB2 variants significantly increased the risk of MBC (OR, 6.6; p = 0.01) (77).…”

Section: Palb2 and Breast Cancermentioning

confidence: 99%

Molecular Mechanisms of PALB2 Function and Its Role in Breast Cancer Management

Zhou

Zhang

et al. 2020

Front. Oncol.

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Partner and localizer of BRCA2 (PALB2) is vital for homologous recombination (HR) repair in response to DNA double-strand breaks (DSBs). PALB2 functions as a tumor suppressor and participates in the maintenance of genome integrity. In this review, we summarize the current knowledge of the biological roles of the multifaceted PALB2 protein and of its regulation. Moreover, we describe the link between PALB2 pathogenic variants (PVs) and breast cancer predisposition, aggressive clinicopathological features, and adverse clinical prognosis. We also refer to both the opportunities and challenges that the identification of PALB2 PVs provides in breast cancer genetic counseling and precision medicine.

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“…Indeed, different studies have been carried out through the European continent to determine the role and the implication of BRCA1 and BRCA2 genes in BC, as well as detect novel mutations [ 50 – 72 ]. Other genes have been studied in both African and European continents and revealed to be associated with BC, such as CHEK2 [ 52 , 65 , 73 – 75 ], TP53 [ 73 , 76 , 77 ], MTHFR [ 78 ], PALB2 [ 79 – 81 ]. Whereas, other genes have been proved involved in BC development solely in Africa such as APOBEC3A, APOBEC3B, ARID1B, NCOR1, SMAD4, MAP3K1, HER2, HER and RAD50 or only in Europe such as RAD51 [ 82 – 84 ], COMT [ 85 , 86 ], CYP17 [ 86 ], MRE11A [ 61 , 87 ], CYP19 [ 87 ] and MDM2 [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

Genetics of breast cancer in African populations: a literature review

Abbad

Baba

Dehbi

et al. 2018

Glob. Health Epidemiol.

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Breast cancer (BC) is one of the most complex, diverse and leading cause of death in women worldwide. The present investigation aims to explore genes panel associated with BC in different African regions, and compare them to those studied worldwide.We extracted relevant information from 43 studies performed in Africa using the following criteria: case-control study, association between genetic variations and BC risk. Data were provided on mutations and polymorphisms associated with BC without fixing a specific date. Case-only studies and clinical trials were excluded.Our study revealed that the majority of African BC genetic studies remain restricted to the investigation of BRCA1 and BRCA2 genes and differences in their mutations spectrum. Therefore, it is necessary to encourage African researchers to characterize more genes involved in BC using methods generating global information such as next-generation sequencing in order to guide specific and more effective therapeutic strategies for the African community.

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Whole‐exome sequencing and targeted gene sequencing provide insights into the role of PALB2 as a male breast cancer susceptibility gene

Cited by 33 publications

References 45 publications

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Insight into genetic susceptibility to male breast cancer by multigene panel testing: Results from a multicenter study in Italy

Molecular Mechanisms of PALB2 Function and Its Role in Breast Cancer Management

Genetics of breast cancer in African populations: a literature review

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