BRCA gene detection for cancer prevention and management in the high risk population / 中华全科医师杂志

Breast cancer susceptibility gene (BRCA) is a tumor suppressor gene. The carriers of BRCA mutation have a significantly higher risk of breast, ovarian, pancreatic, prostate and rectal cancers than the general population. BRCA gene detection can effectively evaluate the risk of relevant malignant tumors. In this article, the recent research progress on the relationship between BRCA gene mutations and related cancers is summarized, and the roles of BRCA gene testing in the prevention and management of relevant malignant tumors are discussed.

MDT Treatment of Small Cell Lung Cancer Complicated with Adenocarcinoma: A Case Report and Literature Review / 中国肺癌杂志

Small cell lung cancer (SCLC) is the most malignant lung cancer with the highest mortality. At present, the first-line standard treatment is still based on Etoposide and Platinum chemotherapy. However, for SCLC that progresses after first-line therapy, the treatment options are still very limited. Since the molecular mechanism of first-line drug resistance of SCLC is still unclear, and the precision medicine strategy after first-line drug resistance is still in the pre-clinical stage. The proportion of secondary biopsy and genetic testing is very low after the progress of first-line treatment of SCLC. In this study, we report a case of a middle-aged woman who was first diagnosed with SCLC. Adenocarcinoma with sensitive gene mutations and repeated changes of small cell carcinoma were detected by multiple biopsies during the course of the disease, suggesting that the patient may be a special subtype of SCLC - mixed SCLC (M-SCLC). In this case, the patient has been treated with radiotherapy and chemotherapy, immunotherapy and targeted therapy successively, and the survival time has reached 2 years and 8 months. Through the case report and literature review retrospectively, this study aimed to explore the part patients may start to present hybrid histopathologic types or tissue type change after treatment of SCLC. Biopsy pathologic histology and genetic testing is necessary after disease progression to look for potential therapeutic targets, so as to give precise treatment based on molecular markers detection results and provide the patient with the benefit of survival for as long as possible.
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Screening for thalassemia and analysis of gene test results in 41 026 couples of childbearing age in Quanzhou City Fujian Province / 中华地方病学杂志

Objective To investigate the screening and gene test of thalassemia in couples of childbearing age in Quanzhou City Fujian Province.Methods A prospective design was used to collect 41 026 pairs of marriage and excellent blood samples from 12 counties in Quanzhou City,Fujian Province from July 2017 to July 2018.To analyze screened the genetic test results and genotyping of positive thalassemia couples.Firstly,the erythrocyte mean corpuscular volume (MCV) and erythrocyte mean corpuscular hemoglobin (MCH) were used for primary screening.Both sides of the couple were performed hemoglobin electrophoresis when at least one of the couples was screened positive.Couples were performed thalassemia gene detection when blood routine or hemoglobin electrophoresis of the couples was positive.The characteristics of genotypes,homologous carriers and distribution of gene mutations in Quanzhou City were analyzed.Results Among 41 026 couples of childbearing age,4 470 couples had abnormal blood routine examination results in at least one of the couples,the rate of positive screening was 10.90％.There were 952 couples who represented abnormal blood routine or hemoglobin abnormal electrophoresis.Totally 658 cases were diagnosed as thalassemia after thalassemia gene detection,and the diagnosis rate was 34.56％.Totally 493 cases of α-thalassemia were detected,and the higher genotypes were:--SEA/αα,-α3.7/αα and ααQS/αα;and 155 cases of β-thalassemia were detected,and the higher genotypes were:IVS-Ⅱ-654/N,CD41-42/N,CD17/N,βE/N,-28/N;10 cases of α complex β thalassemia were detected.Totally 56 high-risk couples with homologous thalassemia gene were detected,including 50 pairs of homologous α-thalassemia,4 pairs of homologous β-thalassemia,and 2 pairs of homologous couples with α complex β thalassemia.The rate of diagnosis and detection rate of homologous thalassemia in different counties of Quanzhou were quite different (x2 =41.939,21.129,P ＜ 0.05).Among them,the rate of diagnosis in Dehua County was the highest (53.13％,85/160),followed by Yongchun County (39.38％,63/160) and Nan'an City (37.73％,123/326).In addition,the detection rate of homologous thalassemia in Dehua County was the highest (15.00％,12/80),followed by Anxi County (8.44％,13/154) and Yongchun County (7.50％,6/80).Conclusions The incidence of thalassemia in couples of childbearing age in Quanzhou is higher,mainly due to α-thahssemia.The high-risk type of homologous carrier is present in α-thalassemia,which should be paid attention to the prevention and control of thalassemia.

Attention should be paid to hereditary ovarian cancer / 西安交通大学学报(医学版)

The occurrence of 20 to 25 percent of ovarian cancer is associated with genetic factors.Hereditary ovarian cancer includes genetic ovarian cancer and familial ovarian cancer.The genetic characteristics of tumors and the development of gene testing technology make it possible to detect tumor-related mutational genes by testing the gene of the proband and thus identify the other family members at risk and intervene early so as to realize early prevention and detection of the cancer.The paper reviews the genetic basis and pathogenesis of hereditary ovarian cancer as well as methods of detecting mutational genes, management of the proband, problems at present, and disease prevention for high-risk individuals.It stresses that we should pay attention to hereditary ovarian cancer in clinical work, identify the proband, and make comprehensive evaluation of risks of the patients` relatives so as to provide individualized guidance and carry out the concept of precision medicine.

The genetic basis and clinical application of heterogeneity of breast cancer / 中华外科杂志

Breast cancer is comprised of a group of heterogeneous diseases that differ significantly in their clinic-pathologic characteristics and molecular profiles. For many years, this disease has been classified according to the integral clinicopathological factors, to provide a dictates for institution of therapeutic approach. Over the past decades, several waves of technology have advanced the characterization of mutations in cancer genomes, especially the emerge and application of high-through next-generation sequencing technique. It has enabled systematic characterization of the full repertoire of molecular diversity of cancer cells, and yielded substantial insights into the genomic mutation and evolution, the intrinsic genetic nature of biology and heterogeneity in human cancer. This article aims to describe recent advances and application of advanced technologies towards the identification of heterogeneity of breast cancer.

Multi-gene assay profiling testing and individualized therapy in breast cancer / 中华外科杂志

Breast cancer is a heterogenetic disease. Multi-gene assay profiling can classify breast cancer into several molecular subtypes, which is better to predict disease prognosis and treatment response. Two prospective clinical trials validated the prognosis predictive value of 21 gene recurrence score and MammaPrint in early breast cancer, than to decrease the prescription of adjuvant chemotherapy and avoid side effect of chemotherapy. New multi-gene assay profiling integrating clinic-pathological factors or reflecting disease development and metastasis can help us predict disease outcome better, thus to achieve individualized therapy in breast cancer.

Hot topics of circulating tumor DNA testing in breast cancer / 中华外科杂志

The progress of gene detection technologies represented by next generation sequencing (NGS) and digital PCR laid a foundation for studies of circulating tumor DNA (ctDNA) in breast cancer. In 2014, the NGS workgroup organized by the College of American Pathologists (CAP) published the College of American Pathologists′ Laboratory Standards for Next-Generation Sequencing Clinical Tests, which provides a blueprint for the standardization of gene testing. In 2015, the Guidelines for Diagnostic Next-generation Sequencing published by the European Society of Human Genetics claimed that NGS is unacceptable in clinical practice before studies guided by guidelines are approved. Although existing studies show the benefits of ctDNA testing in disease monitoring and prognosis analyzing, we have a ways to go to normalize the procedure and build strict detection criteria.

Multiple primary triple cancer of the thyroid breast and lung and 21-gene expression detection: A case report / 肿瘤

Objective: To discuss the clinical and pathological features and the diagnosis and therapy of multiple primary triple cancers of thyroid, breast and lung. Methods: The medical records of a case of multiple primary triple cancers of thyroid, breast and lung were reviewed retrospectively, and the clinicopathological features as well as the diagnosis and therapy were analyzed. Results: Multiple primary triple cancers of this case were performed with surgical operation. Because this case had lymph node-negative and estrogen receptor-positive early-stage breast cancer, the 21-gene detection was performed, and the recurrence score showed low risk, so the case didn't need chemotherapy treatment. Conclusion: The principle of treatment and the prognosis of multiple primary cancers are similar to those of single cancer, and the treatment options for patients with early-stage breast cancer with estrogen receptor-positive and lymph node-negative may refer to the 21-gene recurrence score system.

Study on Gastric Cancer Susceptibility Gene Profiling and Risk Assessment in An Area in Shanghai / 胃肠病学

significant for the precaution of gastric cancer risk population. Aims:To explore gastric cancer susceptibility gene profiling in an area in Shanghai,and to assess the risk of gastric cancer susceptibility. Methods:A total of 152 patients with primary gastric cancer at Shanghai Pudong Hospital were enrolled,and 152 demographic characteristics matched patients with non-gastrointestinal diseases,non-tumor were served as controls. Gene polymorphism was determined by allele specific polymerase chain reaction. Susceptibility gene of gastric cancer was screened. Multiple genes interactions were analyzed and multiple genes risk was evaluated by DEMCHUK model. Results:Univariate analysis showed that CYP2E1,NAT2M1,NAT2M2,NAT2,XRCC1194,MTHFRA1298C,VDR TaqⅠ were susceptibility genes of gastric cancer. Multivariate analysis showed that CYP2E1(C1/ C1),NAT2M1(T/ T),NAT2M2(A/ A),XRCC1194( T/ T)and MTHFRA1298C(A/ C)were susceptibility genotypes. Synergistic effect was found between genes except MTHFRA1298C (A/ C)with NAT2M1(T/ T)and NAT2M2(A/ A)(P ﹤0. 05). Multiple genes risk analysis showed that combination OR of multiple genes was highly correlated with gene frequency,and the risk of gastric cancer was increased with the increasing number of susceptibility genes. Conclusions:CYP2E1(C1/ C1),NAT2M1(T/ T),NAT2M2( A/ A),XRCC1194( T/ T) and MTHFRA1298C( A/ C) are susceptibility genotypes of gastric cancer. Carrying multiple susceptibility genes can significantly increase the risk of gastric cancer.

Children with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome：two cases report / 临床儿科杂志

ObjectiveTo discuss the clinical features, diagnosis and treatment of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome in children.Methods The clinical features and treatment process of two children with MELAS were retrospectively analyzed.ResultsThe main clinical features of MELAS were stroke-like epi-sodes, seizure, visual anomaly and lactic acidosis. Cephalic MRI ifndings performed during episode periods were in accord with the typical radiographic features of MELAS. Gene testing on the two children and their mothers showed the point mutation of A3243G in mitochondrial genome. The symptoms were improved signiifcantly after energy supply and corticosteroid treatment. Conclusions MELAS syndrome is easy to be misdiagnosed due to the varied clinical features. The diagnosis depends on the musclebiopsy and gene testing. Corticosteroid therapy is effective for MELAS syndrome.

Relationship between positive rate of EBV and HCMV testing with patients′age in 179 cases of leukemia / 国际检验医学杂志

Objective To understand the relationship between the positive rate of Epstain‐Barr virus (EBV) and human cyto‐megalovirus (HCMV) nucleic acid detection with the age in the patients with aplastic anemia ,acute lymphoblastic leukemia and my‐eloid leukemia .Methods The patients clinically diagnosed as aplastic anemia ,acute lymphoblastic leukemia ,and myeloid leukemia after bone marrow puncture in the Navy General Hospital from January 2012 to December 2013were collected as the research sub‐jects .the nucleic acid test kit from DAAN Gene Company was adopted for conducting the EBV and HCMV nucleic acid testing and analyzing the relationship between the positive rate of the EBV and HCMV infection with the patient′s age .Results There were different testing positive rate among 3 kinds of hematonosis .As a whole ,the positive rate of HCMV was lower than that of EBV (15 .8% vs .43 .7% ) .The EBV nucleic acid detection positive rate had statistically significant difference among different ages of pa‐tients with aplastic anemia and myeloid leukemia .(P< 0 .01) .Conclusion For children patients with aplastic anemia disease and myeloid leukemia ,more attention should be paid to monitoring of EBV and HCM V nucleic acid .

Establishment and application of a MassARRAY platform-based method to detect multiplex genetic mutations in lung cancer / 中国肿瘤临床

Objective:To establish a method based on the iPLEX analysis of MassARRAY mass spectrometry platform to detect multiplex genetic mutations among Chinese lung cancer patients. Methods:We reviewed the related literature and data of lung cancer treatments. We also determined 99 mutation hot spots in 13 target genes, namely, EGFR, KRAS, ALK, FGFR1, FGFR2, FGFR3, PIK3CA, BRAF, PTEN, MET, ERBB2, AKT1, and STK11, which are closely related to the pathogenesis, drug resistance, and metastasis of lung cancer and are associated with relevant transduction pathways. A total of 297 primers comprising 99 paired forward and reverse amplification primers and 99 matched extension primers were designed by using Assay Design in accordance with the mutation label and format requirements of the MassARRAY platform. The detection method was established by analyzing eight cell lines and six lung cancer specimens;the proposed method was then validated through comparisons with a LungCarta kit. The sensitivity and specificity of the proposed method were evaluated by directly sequencing EGFR and KRAS genes in 100 lung cancer cases. Results:The proposed method could detect multiplex genetic mutations in the lung cancer cell lines, and this finding is consistent with that observed using previously reported methods. The proposed method could also detect such mutations in clinical lung cancer specimens;this result is also consistent with that observed by using the LungCarta kit. However, an FGFR2 mutation was detected only by using the proposed method. The measured sensitivity and specificity were 100%and 96.3%, respectively. Conclusion:The proposed MassARRAY technology-based method could detect multiplex genetic mutations among Chinese lung cancer patients. Indeed, the proposed method can be potentially applied to detect mutations in cancer cells.

Post-Genomic Era:Research and Development / 中国医学伦理学

With the Human Genome Program coming to a successful end,the post genomic era has arrived in which the research of post genomic program is developing quickly.In this paper,the developing trend of the functional genomics research in post genomic era are discussed,with the contents involved: functional genomics,functional proteomics,pharmacogenomics,gene testing,bioinformatics,comparative genomics,which they are main research fields of post genomic era.In the last part,related ethical,legal and social implications are discussed.