TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Al-Qasem, Abeer J.; Toulimat, Mohamed; Eldali, Abdelmoneim; Tulbah, Asma; Al‐Yousef, Nujoud; Al-Daihan, Sooad; Tassan, Nada Al; Al‐Tweigeri, Taher; Aboussekhra, Abdelilah

doi:10.3892/ol.2011.236

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…These genes include ATM, TP53, CHECK2, PTEN, STK11, PALB2, BRIP, and the RAD51 genes (Merdad et al, ). In fact, the frequency of TP53 mutations among Saudi patients is one of the highest in the world (Al‐Qasem et al, ; Chopra & Kelly, ). Further researches are needed to elucidate the spectrum of mutations in those genes to confirm their association with the increase risk of developing breast cancer in the population.…”

Section: Discussionmentioning

confidence: 99%

Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

Hannan

Keogh

Taha

et al. 2019

Molec Gen & Gen Med

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Background Breast cancer is the most common malignancy in women worldwide. About 5%–10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next‐generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes. Methods Twenty‐five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon–intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS. Results We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer. Conclusion Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives.

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Section: Discussionmentioning

confidence: 99%

Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

Hannan

Keogh

Taha

et al. 2019

Molec Gen & Gen Med

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“…Also, an excess of G:C>A:T transitions (49%) at non-CpG sites was noted, suggesting exposure to particular environmental carcinogens such as N-nitroso compounds. 126 In addition, several single nucleotide polymorphisms in Arab patients seem to be specific to the indigenous populations and could be associated with increased risk of breast cancer. Examples include: the p.Pro72Pro in the TP53 gene and the c.309GG in the MDM2 gene in Saudi women, the c.-251A IL8 allele in Tunisian women, and the c.1298A>C DNA polymorphism in the MTHFR gene in patients of Syrian ancestry.…”

Section: Neoplasmsmentioning

confidence: 99%

Arab gene geography: From population diversities to personalized medical genomics

Tadmouri

Sastry

Chouchane

2014

Global Cardiology Science and Practice

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Genetic disorders are not equally distributed over the geography of the Arab region. While a number of disorders have a wide geographical presence encompassing 10 or more Arab countries, almost half of these disorders occur in a single Arab country or population. Nearly, one-third of the genetic disorders in Arabs result from congenital malformations and chromosomal abnormalities, which are also responsible for a significant proportion of neonatal and perinatal deaths in Arab populations. Strikingly, about two-thirds of these diseases in Arab patients follow an autosomal recessive mode of inheritance. High fertility rates together with increased consanguineous marriages, generally noticed in Arab populations, tend to increase the rates of genetic and congenital abnormalities. Many of the nearly 500 genes studied in Arab people revealed striking spectra of heterogeneity with many novel and rare mutations causing large arrays of clinical outcomes. In this review we provided an overview of Arab gene geography, and various genetic abnormalities in Arab populations, including disorders of blood, metabolic, circulatory and neoplasm, and also discussed their associated molecules or genes responsible for the cause of these disorders. Although studying Arab-specific genetic disorders resulted in a high value knowledge base, approximately 35% of genetic diseases in Arabs do not have a defined molecular etiology. This is a clear indication that comprehensive research is required in this area to understand the molecular pathologies causing diseases in Arab populations.

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“…The risk originates from heritable mutations in specific genes. 8,9 The type of cancer is dependent on the mutated gene. Hereditary breast and ovarian cancers originate from BRCA1 and/or BRCA2 gene mutations that significantly increase the likelihood of developing breast, ovarian, prostate and other types of cancer.…”

Section: Introductionmentioning

confidence: 99%

“…1,10 Patients with Li-Fraumeni syndrome, characterised by TP53 mutations, have a heightened risk of cancer before age 30, and are almost guaranteed to suffer from cancer by the age of 60. 8,[11][12][13] Carriers of cancer syndrome associated genes also have a higher risk of multiple malignancies and rare cancers, and are more likely to develop cancer at a younger age.…”

Section: Introductionmentioning

confidence: 99%

Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

et al. 2020

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The study of hereditary cancer, which accounts for~10% of cancer cases worldwide is an important subfield of oncology. Our understanding of hereditary cancers has greatly advanced with recent advances in sequencing technology, but as with any genetic trait, gene frequencies of cancer-associated mutations vary across populations, and most studies that have located hereditary cancer genes have been conducted on European or Asian populations. There is an urgent need to trace hereditary cancer genes across the Arab world. Hereditary disease is particularly prevalent among members of consanguineous populations, and consanguineous marriages are particularly common in the Arab world. There are also cultural and educational idiosyncrasies that differentiate Arab populations from other more thoroughly studied groups with respect to cancer awareness and treatment. Therefore, a review of the literature on hereditary cancers in this understudied population was undertaken. We report that BRCA mutations are not as prevalent among Arab breast cancer patients as they are among other ethnic groups, and therefore, other genes may play a more important role. A wide variety of germline inherited mutations that are associated with cancer are discussed, with particular attention to breast, ovarian, colorectal, prostate, and brain cancers. Finally, we describe the state of the profession of familial cancer genetic counselling in the Arab world, and the clinics and societies dedicated to its advances. We describe the complexities of genetic counselling that are specific to the Arab world. Understanding hereditary cancer is heavily dependent on understanding population-specific variations in cancer-associated gene frequencies.

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TP53 genetic alterations in Arab breast cancer patients: Novel mutations, pattern and distribution

Cited by 16 publications

References 35 publications

Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next‐generation sequencing

Arab gene geography: From population diversities to personalized medical genomics

Familial/inherited cancer syndrome: a focus on the highly consanguineous Arab population

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