title: Recurrent TP53 missense mutation in cancer patients of Arab descent.
abstract: Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c.541C>T, R181C (rs587782596), in two women from unrelated Arab families. The two probands were diagnosed with breast cancer at a young age (27 and 34 years) and had significant family history spanning a wide range of tumors (breast cancer (BC), papillary thyroid cancer, glioblastoma multiform (GBM), colon cancer and leukemia). The R181C variant is expected to disrupt p53 at the ASPP2 binding domain but not the DNA binding domain and is defined by Clinvar as likely pathogenic and in HGMD as disease mutation. We further tested 85 unrelated Arab cancer patients and father of a BC carrier patient for TP53 c.541C>T using a real time polymerase chain reaction (RT-PCR) approach and identified four additional carriers, two with BC one with lung cancer, and the father of a BC carrier patient, diagnosed with GBM. Another carrier suffering from BC was identified using a Myriad panel, suggesting a recurrent mutation in this population with a frequency of 5/42 (11.9%) of our selected BC patients. We suggest testing Arab women with a breast cancer at a young age, Arab patients with multiple malignancies, or with suggestive family history for TP53 c.541C>T.
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Aviad
authors.initials: A
authors.lastname: Zick
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Sherri
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Frohlinger
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.affiliation: Department of Human Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Naama
authors.initials: N
authors.lastname: Zvi
authors.affiliation: Department of Human Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Morasha
authors.initials: M
authors.lastname: Plaser
authors.affiliation: Department of Human Genetics and Metabolic Diseases, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Eilat
authors.initials: E
authors.lastname: Avital
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Shani
authors.initials: S
authors.lastname: Breuier
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Firase
authors.initials: F
authors.lastname: Elian
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Azzam
authors.initials: A
authors.lastname: Salah
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Goldberg
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120, Jerusalem, Israel. Tamary@hadassah.org.il.
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018912:Arabs / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics; D002291:Carcinoma, Papillary; D003110:Colonic Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D005220:Fathers; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D005909:Glioblastoma / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007938:Leukemia / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Arab; Breast; Cancer; Mutation; TP53