Mehrgou Amir, Akouchekian Mansoureh, Hemati Simin
Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Oncology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Med J Islam Repub Iran. 2018 Sep 17;32:87. doi: 10.14196/mjiri.32.87. eCollection 2018.
Breast cancer is one of the most common cancers among Iranian women whose relationship with mutation status in BRCA1 is previously approved. Therefore, screening of the most mutated exons in BRCA1 in hereditary breast cancer patients provides beneficial information about the main disease-causing reason. A total of 14 Iranian hereditary breast cancer patients participated in this case series study. DNA was extracted from patients' blood samples for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences. Five variants in 4 patients were found, including 1 pathogenic variant in exon 16 (H1686Q, NM_007294.3:c.5058T>A) and 4 novel intronic variants of uncertain significance (NC_000017.11:41228314G>T, NC_000017.11:41228309C>T, NC_000017.11:41228317G>T, and NC_000017.11:41203042G>A) in BRCA1. This study was the first to report 1 rare pathogenic variant in BRCA1 (H1686Q, NM_007294.3: c.5058T>A) in an Iranian family as the main disease-causing reason. Another interesting finding was non-existence of variations in almost all globally-reported and mutated exons in BRCA1. Investigation of these exons in BRCA1 showed the uniqueness of mutation pattern in Iranian breast cancer patients compared to other world regions. Due to the existence of other BRCA1 exons and also other predisposing genes in breast cancer, the main cause of cancer development in other participants might have been put in those exons and genes. We concluded that the most mutated exons in BRCA1 in Iranian population may not be the same as those found in other parts of the world.
乳腺癌是伊朗女性中最常见的癌症之一，其与BRCA1基因的突变状态之间的关系此前已得到证实。因此，对遗传性乳腺癌患者中BRCA1基因最易突变的外显子进行筛查，可为主要致病原因提供有益信息。共有14名伊朗遗传性乳腺癌患者参与了本病例系列研究。从患者血液样本中提取DNA用于聚合酶链反应（PCR）检测。使用水平电泳测定PCR产物的质量。然后，进行测序及测序结果分析，以研究序列中的变异情况。在4名患者中发现了5个变异，包括16号外显子中的1个致病变异（H1686Q，NM_007294.3:c.5058T>A）以及BRCA1基因中4个意义未明的新内含子变异（NC_000017.11:41228314G>T、NC_000017.11:41228309C>T、NC_000017.11:41228317G>T和NC_000017.11:41203042G>A）。本研究首次报道了伊朗一个家族中BRCA1基因的1个罕见致病变异（H1686Q，NM_007294.3:c.5058T>A）为主要致病原因。另一个有趣的发现是，在几乎所有全球报道的BRCA1基因易突变外显子中均未发现变异。对BRCA1基因这些外显子的研究表明，与世界其他地区相比，伊朗乳腺癌患者的突变模式具有独特性。由于BRCA1基因存在其他外显子以及乳腺癌中的其他易感基因，其他参与者患癌的主要原因可能存在于那些外显子和基因中。我们得出结论，伊朗人群中BRCA1基因最易突变的外显子可能与世界其他地区不同。
