Detection of novel infiltrating ductal carcinoma-associated BReast CAncer gene 2 mutations which alter the deoxyribonucleic acid-binding ability of BReast CAncer gene 2 protein.
Background
BReast CAncer gene 2 (BRCA2), a tumor suppressor gene located on chromosome 13q, encodes a 384-kDa protein which activates homologous recombination pathway to repair ssDNA damage.


Aims and Objectives
Keeping in view the high prevalence of breast cancer in Pakistan and significant association of BRCA2 with breast cancer, this project was initiated to investigate the mutational status of BRCA2 in Pakistani breast cancer patients.


Materials and Methods
For this purpose, blood samples of 45 individuals, including 24 female patients (infiltrating ductal carcinoma of breast), who visited Institute of Nuclear Medicine, Oncology and Radiotherapy Hospital and Ayub Medical Complex, Abbottabad, Khyber Pakhtunkhwa, and 21 normal female residents of the area were collected and processed to extract deoxyribonucleic acid (DNA). Different regions of BRCA2 exon 11 were amplified through polymerase chain reaction (PCR), and PCR-amplified products of one (NF45) normal sample and four cancerous (205BC, 215BC, 218BC, 222BC) samples were subjected to DNA sequence analysis.


Results
Analysis of retrieved sequences revealed one novel nonsense mutation in sample 205BC. The observed mutation (delA21587) shifted the normal frame of amino acid (N905I, T906L, K907R, E908N, L909F, H910M, E911K, T912Q, and D913T) in encoded mutant protein and converted L914 into premature termination codon. In case of sample 222BC, another novel substitution mutation (A>G24962) was observed, which altered codon of I (isoleucine) into the codon for M (methionine) at position 2040 in resultant mutant protein.


Conclusion
The results reflect the unique mutational profile of BRCA2 in Pakistani infiltrating ductal carcinoma patients and suggest an extension of study on a large scale.
['Ullah|Lateef|L|', 'Hameed|Yasir|Y|', 'Ejaz|Samina|S|', 'Raashid|Anam|A|', 'Iqbal|Jamshed|J|', 'Ullah|Inam|I|', 'Ejaz|Syeda Abida|SA|']
D000328:Adult D019943:Amino Acid Substitution D024682:BRCA2 Protein D001943:Breast Neoplasms D018270:Carcinoma, Ductal, Breast D016022:Case-Control Studies D018389:Codon, Nonsense D004252:DNA Mutational Analysis D005091:Exons D005260:Female D064368:Healthy Volunteers D006801:Humans D008875:Middle Aged D020125:Mutation, Missense D010154:Pakistan
BReast CAncer gene 2 homologous recombination pathway infiltrating ductal carcinoma nonsense mutation premature termination codon substitution mutation