雅库特年轻乳腺癌患者线粒体基因组的变异性

D. Tikhonov, A. Egorov, M. Golubenko, A. Molokov, V. Belyavskaya, P. Gervas, N. Skryabin
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In this regard, we decided to shift the focus to studying the mitochondrial genome of Sakha BC patients using the sequencing method.The purpose of the study was to identify BC-associated mitochondrial genome variants in Sakha patients.Material and Methods. The study included 14 Sakha patients diagnosed with BC. The median age of the patients was 49 years. DNA isolation was performed using phenol-chloroform extraction. DNA libraries were prepared using the Nextera Flex kit (Illumina, USA).Whole-genome sequencing of the mitochondrial genome was performed on a MiSeq instrument (Illuminа, USA). in the Shared Use Centre of the Research Institute of Medical Genetics, Tomsk National Research Centre of the Russian Academy of Sciences. The results obtained in BC patients were compared with those of control subjects.Results. In Sakha women with BC, 159 mitochondrial genome variants that differed from the human mitochondrial DNA (mtDNA) reference sequence (rCRS) were identified. 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引用次数: 0

摘要

背景。萨哈(雅库特)人是居住在雅库特的西伯利亚土著居民,是全世界乳腺癌(BC)发病率最低的人群之一。雅库特原住民乳腺癌发病率低的情况已有多位学者报道,但迄今为止,造成这一现象的原因尚未完全阐明。应该指出的是,研究降低 BC 风险的因素对于预防 BC 非常重要。在多项研究中,没有发现雅库特人有遗传性 BC,也没有发现与乳腺癌和卵巢癌遗传综合征相关的 BRCA1/2 基因的致病变体。有鉴于此,我们决定将研究重点转向使用测序方法研究萨哈族 BC 患者的线粒体基因组。研究包括 14 名被确诊为 BC 的萨哈族患者。患者的中位年龄为 49 岁。DNA分离采用苯酚-氯仿提取法。线粒体基因组的全基因组测序在俄罗斯科学院托木斯克国家研究中心医学遗传学研究所共享中心的 MiSeq 仪器(Illuminа,美国)上进行。将 BC 患者的结果与对照组的结果进行了比较。结果发现,在萨哈女性 BC 患者中,有 159 个线粒体基因组变异与人类线粒体 DNA(mtDNA)参考序列(rCRS)不同。结果表明,MT-ND1 基因的 m.3736G>A 和 MT-CO1 基因的 m.7279T>C 可能与 BC 有关。首次发现了易导致 BC 的变体(m.10398A>G;m.14783T>C;m.15043G>A;m.15301G>A)。BC发病率低的人群线粒体基因组的一个显著特点是,D310位点多胞嘧啶区长度发生变化的mtDNA变异水平较高。在萨哈族 BC 妇女中首次发现了 D310 位点多胞嘧啶区长度变化的 mtDNA 变异以及 MT-ND1 基因 m.3736G>A 和 MT-CO1 基因 m.7279T>C 的可能致病变异。获得的数据表明,需要使用更多的萨哈病人样本,进一步研究已确定的 mtDNA 变异在 BC 发病中的作用。
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Variability of the mitochondrial genome in young Yakut patients with breast cancer
Background. The Sakha (Yakutia) population, the indigenous population of Siberia living in Yakutia, has one of the lowest rates of breast cancer (BC) incidence worldwide. The low BC incidence among the indigenous population of Yakutia has been reported by several authors, but to date the reasons for this phenomenon have not been fully elucidated. It should be noted that the study of factors that reduce the risk of BC is important for its prevention. In several studies, no hereditary BC was found in the Yakuts, and no pathogenic variants of the BRCA1/2 genes associated with hereditary syndromes of breast and ovarian cancers were found. In this regard, we decided to shift the focus to studying the mitochondrial genome of Sakha BC patients using the sequencing method.The purpose of the study was to identify BC-associated mitochondrial genome variants in Sakha patients.Material and Methods. The study included 14 Sakha patients diagnosed with BC. The median age of the patients was 49 years. DNA isolation was performed using phenol-chloroform extraction. DNA libraries were prepared using the Nextera Flex kit (Illumina, USA).Whole-genome sequencing of the mitochondrial genome was performed on a MiSeq instrument (Illuminа, USA). in the Shared Use Centre of the Research Institute of Medical Genetics, Tomsk National Research Centre of the Russian Academy of Sciences. The results obtained in BC patients were compared with those of control subjects.Results. In Sakha women with BC, 159 mitochondrial genome variants that differed from the human mitochondrial DNA (mtDNA) reference sequence (rCRS) were identified. Likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were shown to be associated with BC. For the first time, variants predisposing to BC (m.10398A>G; m.14783T>C; m.15043G>A; m.15301G>A) were identified. A distinctive feature of the mitochondrial genome of populations with a low BC incidence is a high level of mtDNA variants with changes in the length of the polycytosine region in the D310 locus.Conclusion. For the first time, mtDNA variants with changes in the length of the polycytosine tract in the D310 locus and likely pathogenic variants m.3736G>A of the MT-ND1 gene and m.7279T>C of the MT-CO1 gene were identified in Sakha BC women. The data obtained indicate that further studies on the role of the identified mtDNA variants in the development of BC using a larger sample of Sakha patients are required.
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来源期刊
Siberian journal of oncology
Siberian journal of oncology Medicine-Oncology
CiteScore
0.40
自引率
0.00%
发文量
117
审稿时长
8 weeks
期刊介绍: The main objectives of the journal are: -to promote the establishment of Russia’s leading worldwide positions in the field of experimental and clinical oncology- to create the international discussion platform intended to cover all aspects of basic and clinical cancer research, including carcinogenesis, molecular biology, epidemiology, cancer prevention, diagnosis and multimodality treatment (surgery, chemotherapy, radiation therapy, hormone therapy), anesthetic management, medical and social rehabilitation, palliative care as well as the improvement of life quality of cancer patients- to encourage promising young scientists to be actively involved in cancer research programs- to provide a platform for researches and doctors all over the world to promote, share, and discuss various new issues and developments in cancer related problems. (to create a communication platform for the expansion of cooperation between Russian and foreign professional associations).- to provide the information about the latest worldwide achievements in different fields of oncology The most important tasks of the journal are: -to encourage scientists to publish their research results- to offer a forum for active discussion on topics of major interest - to invite the most prominent Russian and foreign authors to share their latest research findings with cancer research community- to promote the exchange of research information, clinical experience, current trends and the recent developments in the field of oncology as well as to review interesting cases encountered by colleagues all over the world- to expand the editorial board and reviewers with the involvement of well-known Russian and foreign experts- to provide open access to full text articles- to include the journal into the international database- to increase the journal’s impact factor- to promote the journal to the International and Russian markets
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