Dey Shatovisha, Marino Natascia, Bishop Kanokwan, Dahlgren Paige N, Shendre Aditi, Storniolo Anna Maria, He Chunyan, Tanaka Hiromi
Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Oncotarget. 2017 Dec 29;9(3):4214-4222. doi: 10.18632/oncotarget.23767. eCollection 2018 Jan 9.
Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls of 28 healthy women. The results showed that the plasma telomeric cfDNA level was lower in unaffected BRCA1&2 mutation carriers than in age-matched controls from non-obese women (BMI < 30), while there was no association between unaffected BRCA1&2 mutation carriers and age-matched controls in obese women (BMI > 30). Moreover, the plasma telomeric cfDNA level applied aptly to the Tyrer-Cuzick model in non-obese women. These findings suggest that circulating cfDNA may detect dysfunctional telomeres derived from cells with BRCA1&2 mutations and, therefore, its level is associated with breast cancer susceptibility. This pilot study warrants further investigation to elucidate the implication of plasma telomeric cfDNA levels in relation to cancer and obesity.
血浆游离DNA（cfDNA）是一种在血液中循环的小DNA片段，其来源于非肿瘤细胞和肿瘤细胞。先前的一项研究表明，与对照组相比，散发性乳腺癌患者的血浆端粒cfDNA水平降低。包括BRCA1和BRCA2（BRCA1&2）在内的肿瘤抑制基因产物在端粒维持中起重要作用。在本研究中，我们假设血浆端粒cfDNA水平与BRCA1&2基因的突变状态相关。为了验证这一假设，我们进行了基于血浆端粒cfDNA定量PCR（qPCR）的检测，以比较28名携带BRCA1&2突变的女性与28名年龄匹配的健康女性对照组。结果显示，未受影响的BRCA1&2突变携带者的血浆端粒cfDNA水平低于非肥胖女性（BMI<30）的年龄匹配对照组，而在肥胖女性（BMI>30）中，未受影响的BRCA1&2突变携带者与年龄匹配对照组之间没有关联。此外，血浆端粒cfDNA水平适用于非肥胖女性的Tyrer-Cuzick模型。这些发现表明，循环cfDNA可能检测到源自具有BRCA1&2突变的细胞的功能失调端粒，因此，其水平与乳腺癌易感性相关。这项初步研究值得进一步调查，以阐明血浆端粒cfDNA水平与癌症和肥胖的关系。
