PALB2 germline mutations in a large cohort of Middle Eastern breast-ovarian cancer patients.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 05 2023
Historique:
received: 10 10 2022
accepted: 05 05 2023
medline: 15 5 2023
pubmed: 12 5 2023
entrez: 11 5 2023
Statut: epublish

Résumé

The PALB2 gene is a breast cancer (BC) and ovarian cancer (OC) predisposition gene involved in the homologous recombination repair pathway. However, the prevalence and clinicopathological association of PALB2 pathogenic/likely pathogenic (PV/LPV) variants in Middle East is still not fully explored. Total 918 BC/OC patients from Saudi Arabia were selected for PALB2 mutations screening using capture sequencing technology. Five heterozygous PVs or LPVs were identified in six cases, accounting for 0.65% (6/918) of entire cohort. Two cases (33.3%) harbored PVs and four cases (66.7%) carried LPVs. Four PVs/LPVs (80%) were frameshift along with one novel splicing LPV (c.2835-2_2835-1delinsTT). One recurrent LPV (c.3425delT: p.L1142fs) was identified in two cases. All six affected carriers have breast cancer diagnosis with median age of 39.5 years (range 34-49 years). Only two cases (33%) have documented family history of cancer. Breast cancer phenotype was invasive ductal unilateral cancer in all cases with 66.7% of hormone receptor positive and 16% of triple negative tumors. Germline PVs/LPVs in the PALB2 gene were observed in low frequency of 0.65% in Saudi BC and/or OC. Our study confirms one recurrent LPV and one novel LPV in Saudi breast cancer patients.

Identifiants

pubmed: 37169825
doi: 10.1038/s41598-023-34693-9
pii: 10.1038/s41598-023-34693-9
pmc: PMC10175539
doi:

Substances chimiques

Fanconi Anemia Complementation Group N Protein 0
PALB2 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

7666

Informations de copyright

© 2023. The Author(s).

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Auteurs

Abdul K Siraj (AK)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Rong Bu (R)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Sandeep Kumar Parvathareddy (SK)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Kaleem Iqbal (K)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Saud Azam (S)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Zeeshan Qadri (Z)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Maha Al-Rasheed (M)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Wael Haqawi (W)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Mark Diaz (M)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Ingrid G Victoria (IG)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia.

Ismail A Al-Badawi (IA)

Department of Obstetrics-Gynecology, King Faisal Specialist Hospital and Research Center, Riyadh, 11211, Saudi Arabia.

Asma Tulbah (A)

Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.

Fouad Al-Dayel (F)

Department of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.

Dahish Ajarim (D)

Oncology Center, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.

Khawla S Al-Kuraya (KS)

Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia. kkuraya@kfshrc.edu.sa.

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Classifications MeSH