Screening for Del 185 AG and 4627C&gt;A BRCA1 Mutations in Breast Cancer Patients from Lahore, Pakistan

Aziz, Faiza; Fatima, Warda; Mahmood, Saqib; Khokher, Samina

doi:10.7314/apjcp.2016.17.4.1725

Cited by 3 publications

(3 citation statements)

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“…The founder mutations are expected in consanguineous populations like the present one. Although we did not find any recurrent mutation in the present cohort, comparison with previously published reports indicated that 185delAG may be a founder mutation ( Liede et al, 2002 ; Rashid et al, 2006 ; Moatter et al, 2011 ; Ahmad et al, 2012 ; Aziz et al, 2016 ; Rashid et al, 2016 ; Rashid et al, 2017 ; Torres et al, 2017 ).…”

Section: Discussioncontrasting

confidence: 75%

“…In Pakistani population, some studies have analyzed BRCA1 and BRCA2 mutations ( Liede et al, 2002 ; Rashid et al, 2006 ; Moatter et al, 2011 ; Ahmad et al, 2012 ; Aziz et al, 2016 ; Rashid et al, 2016 ; Rashid et al, 2017 ; Torres et al, 2017 ), mainly through conventional methodologies. In case of other putative breast cancer susceptibility genes, scarce or no data is available from this region ( Khaliq et al, 2000 ; Baig et al, 2011 ; Rashid et al, 2014 ; Baloch et al, 2016 ; Rashid et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations

et al. 2022

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Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately and accurately in highly-consanguineous Pakistani population. In the present discovery case series, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy gender-matched controls. The clinico-pathological features were evaluated by descriptive analysis and Pearson χ2 test (with significant p-value <0.05). The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the analyses were stratified on the basis of age (≤40 years vs. >40 years) and ethnicity. The breast cancer gene panel assay was carried out by BROCA, which is a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (≤40 years) was higher in Sindhis (n = 12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grade III (50%), tumor size 2–5 cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients, which was not significantly associated with younger age or any particular ethnicity. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of hereditary-based preventive and treatment strategies against breast cancers in Pakistani population.

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Section: Discussioncontrasting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations

et al. 2022

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“…Regarding family history, patient in present study reported to have negative family history for any kind of cancer as Liede et al , 2002 16 also reported the victims with this mutation had negative family history for such cancers. Previous studies on Pakistani population also tried to find relation with ethnicity as Rashid et al, 2006 17 reported BRCA1 - 185 Del AG in two of the pathan patients while Liede et al , 2006 16 and Aziz et al , 2016 18 reported this mutation in patient with Punjabi ethnicity and currently it was also observed in patient with Punjabi ethnicity. In the two prior studies on Pakistani population that included exon-2 in investigation none of the patients found to be positive for 185 delAG .…”

Section: Discussionmentioning

confidence: 99%

Association of BRCA1 185 del AG with early age onset of breast cancer patients in selected cohort from Pakistani population

et al. 2018

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Background & Objective:Large spectrum of pathogenic BRCA mutations is known as a major cause of hereditary breast ovarian cancer in human all over the world. The objective of present study was to find out the association of mutations185-del-AG and 185Ins.A at BRCA1 exon-2 with age of onset and family history of gynecological cancer among the selected cohort of breast cancer patients in Pakistani population and to provide guidelines for treatment strategies.Methods:For the present study 115 subjects were recruited from different hospitals of Punjab, Pakistan, during May, 2017 to February, 2018. The inclusion criteria were age ≥30, without any previous BRCA testing and willingness to participate in present study. Subjects were interviewed for various demographic factors. Out of 115 subjects, 46 were selected on the basis of findings of previous studies and approximately 3 ml of blood was collected in EDTA coated vials for analysis of BRCA1 exon-2. Column based DNA extraction was performed by using commercial kit and exon specific primers were used to amplify BRCA1 exon 2 and PCR products were sent for sequencing to Eurofins Genomics. Sequences were analyzed through the BLAST program at National Center for Biotechnology Information (NCBI) and Bio Edit software. Accession numbers were obtained on submission of sequences in GenBank.Results:BRCA1-185-del AG mutation was found in one of the breast cancer patient who was 33 years of age at diagnosis. None of the samples revealed positive results for BRCA1-185 Ins. A.Conclusion:BRCA1-185 Del AG mutation has association with early age onset of breast cancer. The direct sequencing is very useful approach for BRCA analysis and exon specific selected cohort from Pakistani population.

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Germline Mutation Analysis in Sporadic Breast Cancer Cases with Clinical Correlations

Ajaz

Zaidi

et al. 2021

Preprint

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Demographics for breast cancers vary widely among nations. The frequency of germline mutations in breast cancers, which reflects the hereditary cases, has not been investigated adequately in Pakistani population. In the present study, germ-line mutations in twenty-seven breast cancer candidate genes were investigated in eighty-four sporadic breast cancer patients along with the clinical correlations. The germ-line variants were also assessed in two healthy controls. The most frequent parameters associated with hereditary cancer cases are age and ethnicity. Therefore, the clinico-pathological features were evaluated by descriptive analysis and Pearson χ2 test (with significant p-value <0.05). The analyses were stratified on the basis of age (<40 years vs >40 years) and ethnicity. The breast cancer gene panel assay was carried out by a genomic capture, massively parallel next generation sequencing assay on Illumina Hiseq2000 assay with 100bp read lengths. Copy number variations were determined by partially-mapped read algorithm. Once the mutation was identified, it was validated by Sanger sequencing. The ethnic analysis stratified on the basis of age showed that the frequency of breast cancer at young age (<40 years) was higher in Sindhis (n=12/19; 64%) in contrast to patients in other ethnic groups. Majority of the patients had stage III (38.1%), grades II and III (46.4%), tumor size 2-5cm (54.8%), and invasive ductal carcinoma (81%). Overall, the analysis revealed germ-line mutations in 11.9% of the patients. The mutational spectrum was restricted to three genes: BRCA1, BRCA2, and TP53. The identified mutations consist of seven novel germ-line mutations, while three mutations have been reported previously. All the mutations are predicted to result in protein truncation. No mutations were identified in the remaining twenty-four candidate breast cancer genes. The present study provides the framework for the development of preventive and treatment strategies against breast cancers in Pakistani population.

show abstract

Screening for Del 185 AG and 4627C>A BRCA1 Mutations in Breast Cancer Patients from Lahore, Pakistan

Cited by 3 publications

References 10 publications

Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations

Germline Mutation Analysis in Sporadic Breast Cancer Cases With Clinical Correlations

Association of BRCA1 185 del AG with early age onset of breast cancer patients in selected cohort from Pakistani population

Germline Mutation Analysis in Sporadic Breast Cancer Cases with Clinical Correlations

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