Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis / 中华预防医学杂志

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Identification of two novel mitochondrial DNA deletions induced by ionizing radiation / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We identify ionizing radiation-induced mitochondrial DNA (mtDNA) deletions in human lymphocytes and their distribution in normal populations.</p><p><b>METHODS</b>Long-range polymerase chain reactions (PCR) using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy (60)Co γ-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy (60)Co γ-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated.</p><p><b>RESULTS</b>Two mtDNA deletions, a 7455-bp deletion (nt475-nt7929 in heavy strand) and a 9225-bp deletion (nt7714 -nt369 in heavy strand), occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for (60)Co γ-rays irradiated human peripheral blood cells.</p><p><b>CONCLUSION</b>Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors' age, but was independent of gender.</p>

Further strengthen the surveillance of infectious diseases / 中华检验医学杂志

Human history has never seen so many infectious diseases as in recent times and human being has to face this great challenge threaten public health.The increased global population,increased travel,human-induced global changes,poverty and the breakdown of public health measures,all of these factors make that novel infectious diseases can emerge in any part of the world at any time.In this article,we point out some shortages in diagnosis and screening the infectious diseases in the laboratory,emphasize the importance of surveillance,finally give some suggestions about how to improve the current ability to detect, prevent and treat the infectious diseases.