Advances in genetics and prevention of monogenic global developmental delay and intellectual disability / 中华围产医学杂志

Global developmental delay/intellectual disability (GDD/ID) is an enormous group of neurodevelopmental disorders with diverse clinical and genetic heterogeneity. The estimated prevalence of GDD/ID was 1%-3%, affecting about 150 million people. GDD/ID is one of the leading causes of disability in children worldwide. The causes of GDD/ID are complex, comprising genetic and environmental factors. It is often co-morbid with a variety of psychiatric behavioral disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Owing to the improvement of genetic technology, monogenic GDD/ID has been one of the hot-spot research in genomic era, and the relevant preventive measures deserve extensive attention. In this review, we summarized the advances in genetics and prevention of monogenic GDD/ID.

Caracterización molecular de pacientes con cáncer colorrectal / Molecular characterization of colorectal cancer patients

Introducción. El cáncer colorrectal tiene una alta incidencia en la población mundial. Diversas vías moleculares están involucradas en su desarrollo, entre ellas, la inestabilidad cromosómica, la inestabilidad microsatelital y la epigenética. Objetivo. Hacer la caracterización molecular de 44 individuos con cáncer colorrectal esporádico. Materiales y métodos. El análisis de mutaciones en los genes APC, KRAS, TP53 y BRAF se hizo mediante secuenciación de Sanger; la inestabilidad microsatelital se determinó mediante electroforesis capilar utilizando cinco marcadores de repetición corta en tándem (Short Tandem Repeat) y el estado de metilación del promotor del gen MLH1 se hizo con la técnica MS-PCR (Methylation-Specific PCR). Resultados. La frecuencia de mutación de los genes APC, KRAS y TP53 fue del 18,1, 25 y 4,5 %, respectivamente; las mutaciones detectadas se localizaron con mayor frecuencia en el colon derecho. La frecuencia de inestabilidad microsatelital fue del 27,2 % y el 73,1 % en los tumores con metilación en el gen MHL1, y el 91,6 % de los tumores con inestabilidad microsatelital presentaba metilación en el gen MLH1. En el grupo de tumores con estabilidad microsatelital, las mutaciones en los genes APC, KRAS y TP53 fueron más frecuentes que en el grupo de tumores con inestabilidad microsatelital. La metilación del gen MLH1 fue la alteración más predominante. Conclusiones. En los pacientes con cáncer colorrectal evaluados se demostró la presencia de alteraciones moleculares en las diferentes vías genéticas, las cuales son comunes en su carcinogénesis. Los pacientes presentaron un perfil de mutaciones diferente al de otras poblaciones. Los hallazgos obtenidos en este estudio confirman la heterogeneidad molecular descrita en el desarrollo del cáncer colorrectal.

Introduction: Colorectal cancer has a high incidence in the world population. Different molecular pathways, such as chromosomal instability, microsatellite instability, and epigenetics are involved in its development. Objective: To perform molecular characterization in 44 individuals with sporadic colorectal cancer. Materials and methods: We conducted mutation analyses of the APC, KRAS, TP53 y BRAF genes using Sanger sequencing techniques; microsatellite instability was determined by capillary electrophoresis with five STR genetic markers while the methylation status of the MHL1 promotor gene was analyzed using methylation-specific PCR. Results: APC, KRAS, and TP53 genes mutation frequency was 18.1%, 25%, and 4.5%, respectively; the somatic mutations detected were located more frequently in the right colon. The frequency of microsatellite instability was 27.2% and 73.1% of the tumors had the MHL1 gene methylated while 91.6% of microsatellite instability-positive tumors had the methylated MLH1 gene. The mutation profile of microsatellite stability tumors APC, KRAS, and TP53 genes was more frequent than in the microsatellite instability-positive tumors. The methylation of the MLH1 gene was the most predominant molecular alteration. Conclusions: We identified molecular alterations in different genetic pathways of the colorectal cancer patients evaluated, which are common in the carcinogenesis of this cancer. These patients showed a different mutational profile compared to other populations. Our findings confirm the molecular heterogeneity described in the development of colorectal cancer.

Síndrome de Cornelia de Lange: análise de uma série de 33 pacientes em um centro de referência / Cornelia de Lange syndrome: analysis of a series of 33 patients in an excellence center

Introdução: A Síndrome de Cornelia de Lange (CdLS) (OMIM: 122470) é uma doença genética rara com quadro clínico e fenótipo variáveis, compreendendo um grupo de doenças denominado coesinopatias. Entre suas principais características: deficiência intelectual (DI), baixa estatura, doença do refluxo gastroesofágico (DRGE), hipertricose, dismorfismos faciais e anomalias em membros superiores. O diagnóstico pode ser dificultado nos quadros atenuados. O objetivo do estudo foi determinar os principais achados clínicos e moleculares em uma série de pacientes com o diagnóstico clínico de CdLS.Métodos: Foram avaliados 33 pacientes com diagnóstico clínico e/ou molecular de CdLS (18 sexo feminino e 15 masculino) com idades entre 1 mês e 43 anos. Aplicou-se um escore clínico visando a categorização dos pacientes baseado em Kline et al. (2018). Esta ferramenta utiliza sinais clínicos para determinar as formas clássicas (n: 23), não clássicas (n: 6) e os casos que, apesar de não se enquadrarem nestas categoriais, também deveriam ser testados molecularmente para a síndrome (n: 4).Resultados: Atraso do desenvolvimento/DI, distúrbios de comportamento, déficit de crescimento e DRGE foram as comorbidades mais prevalentes. Entre as dismorfias: sinofris, micrognatia, narinas antevertidas e comissura labial desviada para baixo. Os achados moleculares nos pacientes submetidos ao sequenciamento completo do exoma revelaram 6 variantes em NIPBL (46%), 2 variantes em SMC1A (15%), 1 variante em SMC3, 1 variante em HDAC8, 1 variante em AHDC1 e 2 resultados negativos.Conclusões: Os dados obtidos revelaram uma grande heterogeneidade de apresentação da síndrome. A utilização de escores clínicos podem auxiliar no diagnóstico de CdLS.

Introduction: Cornelia de Lange syndrome (CdLS) (OMIM: 122470) is a rare genetic disease with variable clinical presentation and phenotype, part of a group of disorders termed cohesinopathies. Intellectual disability, growth retardation, gastroesophageal reflux disease, hypertrichosis, facial dysmorphisms, and anomalies of the upper limbs are the most common clinical characteristics. Diagnosis may be difficult, especially in attenuated presentations. The aim of this study was to determine the main clinical and molecular findings in a series of patients with clinical diagnosis of CdLS.Methods: Thirty-three patients with typical clinical and/or molecular diagnosis of CdLS (18 female and 15 male) aged between 1 month and 43 years were evaluated. A clinical score was applied to categorize patients. This tool uses clinical signs to determine the classic (n: 23) and nonclassic (n: 6) forms, in addition to a category to suggest which cases should be molecularly tested for the syndrome (n: 4).Results: Developmental delay/intellectual disability, behavioral disorders, growth retardation, and gastroesophageal reflux disease were the most prevalent comorbidities. Dysmorphic features included synophrys micrognathia, anteverted nostrils, and labial commissure turning downwards. Molecular findings in those who underwent whole exome sequencing revealed 6 variants in NIPBL (46%), 2 variants in SMC1A (15%), 1 variant in SMC3, 1 variant in HDAC8, 1 variant in AHDC1, and 2 negative results.Conclusions: The data revealed a great heterogeneity in the presentation of the syndrome. The use of clinical scores can help in the diagnosis of CdLS.

A case-control study of risk factors for gastritis, gastric intraepithelial neoplasia and gastric cancer in patients with gastroscopic biopsies in Shihezi, Xinjiang / 中华消化内镜杂志

Objective:To explore the risk factors involved in gastritis, gastric intraepithelial neoplasia (GIN) and gastric cancer in Shihezi area.Methods:A total of 7 110 Han nationality patients who underwent gastroscopy at the First Affiliated Hospital of Shihezi University School of Medicine from January 2012 to December 2016 were selected as the research subjects. The data of patients were obtained through medical records and questionnaires. After excluding diseases related to esophagus and duodenum, a total of 4 429 cases were included in the retrospective analysis. Of which, 4 249 were gastritis, 93 were GIN, and 87 were gastric cancer. χ2 test, rank-sum test or Fisher exact probability method were used to analyze the differences of various factors in gastritis, GIN and gastric cancer. Univariate and multivariate logistic regression analysis were used to screen the risk factors for gastritis progression to GIN and gastric cancer. Results:χ2 test and rank sum test showed that there were statistically significant differences in gender, age, history of digestive diseases and distribution of Helicobacter pylori ( HP) infection among the groups of gastritis, GIN and gastric cancer ( P<0.05). The proportion of HP infection decreased gradually with the disease severity. Multivariate logistic regression analysis showed that male ( P<0.001, OR=2.251, 95% CI: 1.461-3.470), elderly ( P<0.001, OR=4.829, 95% CI: 2.241-10.409), a family history of gastric cancer ( P=0.002, OR=3.227, 95% CI: 1.537-6.774) and a history of digestive diseases ( P=0.034, OR=1.644, 95% CI: 1.037-2.607) were independent risk factors for gastritis progression to GIN. Male ( P<0.001, OR=3.254, 95% CI: 2.026-5.225), middle-aged ( P=0.022, OR=2.688, 95% CI: 1.153-6.265) and elderly ( P=0.002, OR=4.734, 95% CI: 1.750-12.807) were independent risk factors for gastritis progression to gastric cancer. In stratified analysis to exclude age and gender, smoking ( P=0.028, OR=4.060, 95% CI: 1.160-14.202) was found to be a risk factor for gastritis progression to GIN in young adults, and obesity ( P=0.032, OR=3.869, 95% CI: 1.121-13.356) was found to be a risk factor for gastritis progression to gastric cancer in women. Conclusion:The degree of HP infection in gastric tissues is negatively correlated with the severity of gastric diseases, suggesting that HP infection may be an early event inducing gastric cancer. Male, the elderly, people with a family history of gastric cancer and a history of digestive diseases, and young smokers in Shihezi are more likely to develop GIN, and male, middle-aged, elderly, and obese women are at increased risk of gastric cancer.

Multi-omics molecular subgrouping of hepatocellular carcinoma and its application in precision diagnosis and treatment / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality in China. In recent years, the application of targeted therapy and immunotherapy has improved the survival rate of HCC patients. However, a significant difference in treatment response is observed among HCC patients due to tumor heterogeneity and a lack of biomarkers to predict efficacy. The advance in proteogenomics-centered multi-omics studies and the development of high-throughput drug screening platforms will help to develop new clinical treatment strategies for HCC and new methods for predicting the efficacy of precision medication, thereby realizing personalized precision diagnosis and treatment.

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma / 医学前沿

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and epigenomic databases, we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants. We identified 3064 credible risk variants for NSCLC, which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites. Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific. Functional annotation and gene-based analysis implicated 894 target genes, including 274 specifics for AD and 123 for SqCC, which were overrepresented in somatic driver genes (ER = 1.95, P = 0.005). Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways, while SqCC genes were homologous recombination deficiency related. Our results illustrate the molecular basis of both well-studied and new susceptibility loci of NSCLC, providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

Circulating tumor cell detection approaching to clinical application / 中华检验医学杂志

As "seeds" of tumor metastasis, circulating tumor cell (CTC) has important clinical application value in early diagnosis, immunotherapy and prognosis evaluation of tumors. With a deep understanding of CTC, its applied research has switched from cell enumeration to the molecular typing and single-cell sequencing. However, the standardization of CTC detection is still at a primary stage, opportunities and challenges coexist. This paper will review the current status and challenges in clinical applications of CTC detection, and make some suggestions for future development.

Intra-tumor genetic heterogeneity in Wilms tumor samples

SUMMARY Childhood renal tumors account for ~7% of all childhood cancers, and most cases are embryonic Wilms' tumors (WT). Children with WT are usually treated by either COG or SIOP. The later treats the children using preoperative chemotherapy, but both have around 90% of overall survival in five years. WT is a genetically heterogeneous group with a low prevalence of known somatic alterations. Only around 30% of the cases present mutation in known genes, and there is a relatively high degree of intra-tumor genetic heterogeneity (ITGH). Besides potentially having an impact on the clinical outcome of patients, ITGH may interfere with the search for molecular markers that are prospectively being tested by COG and SIOP. In this review, we present the proposal of the current UMBRELLA SIOP Study 2017/Brazilian Renal Tumor Group that requires the multi-sampling collection of each tumor to better evaluate possible molecular markers, as well as to understand WT biology

RESUMO Os tumores renais pediátricos correspondem a aproximadamente 7% de todos os tumores infantis, sendo o mais frequente o tumor de Wilms (TW). Crianças com TW são geralmente tratadas seguindo dois distintos protocolos terapêuticos (COG ou SIOP), sendo que no último, os pacientes recebem tratamento quimioterápico pré-operatório. Ambos apresentam sobrevida global em cinco anos em torno de 90%. TW é geneticamente heterogêneo, apresentando baixa prevalência de alterações somáticas conhecidas, com cerca de 30% dos casos apresentando mutações em genes conhecidos e um alto grau de heterogeneidade genética intratumoral (HGIT). Além de potencialmente ter um impacto sobre o desfecho clínico dos pacientes, a HGIT pode interferir na busca de marcadores moleculares que estão sendo testados prospectivamente pelos grupos COG e Siop. Nesta revisão, apresentamos a proposta do atual estudo Umbrella Siop 2017/Grupo de Tumores Renais Brasileiros (GTRB), que orienta a coleta de três diferentes regiões do tumor para melhor avaliar possíveis marcadores moleculares, bem como para compreender a biologia do TW.

The function of long non-coding RNA in the occurrence and development of multiple myeloma / 中国肿瘤临床

Multiple myeloma (MM) is characterized by genetic heterogeneity and is a common secondary hematological malignancy. Many studies have revealed that variation in the number of long non-coding RNAs (lncRNAs) is related to the degree of MM malignancy. Advances in molecular biology technologies, such as fluorescence in situ hybridization, high-throughput sequencing, gene microarrays, and qRT-PCR, have furthered research into cytogenetic malfunction in MM. Eleven newly discovered lncRNAs in MM have been fully interpreted according to the different mechanisms of MM and have the potential to be promising biomarkers for MM diagnosis and therapy.

Single-cell RNA sequencing and its application in dermatology / 中华皮肤科杂志

Single-cell RNA sequencing is a method for transcriptome profiling at the single-cell level,and is a hotspot technology in the field of biological research currently.Compared with the common high-throughput RNA sequencing,single-cell RNA sequencing can distinguish the biological differences between single cells,and identify rare cell populations and subpopulations.This review mainly describes the single-cell RNA sequencing method,summarizes current application of this technique in the field of dermatology,and discusses limitations and prospects of this technique.

Characteristics of diffuse large B-cell lymphoma in Chinese populations / 国际肿瘤学杂志

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma.Generally,it can be divided into two immunological subgroups:germinal center B-cell-like (GCB)and non-germinal center B-cell-like (non-GCB),and they are different both in distribution and prognosis in different populations.And DLBCL has unique genetic characteristics in Chinese populations.With the global advances in personalized medicine,people gradually realize that only personalized therapy could be obtain maximal therapeutic effect for different populations,especially person from different kind of ethnic group.

Research progress on heterogeneity and epigenetics of hepatocellular CarCinoma / 国际外科学杂志

Tumor heterogeneity is one of the common phenomena of malignant tumors, and the heterogeneity of hepatocellular carcinoma is significant. Despite some treatments such as surgical resection, chemotherapy and radiotherapy in the primary phage of hepatocellular carcinoma have been used, the prognosis of patients remains poor, which is closely related to the heterogeneity of hepatocellular carcinoma. Therefore, exploring the heterogeneity of hepatocellular carcinoma has important clinical significance for improving the therapeutic effect of hepatocellular carcinoma. This article reviews the heterogeneity of hepatocellular carcinoma from an epigenetic perspective and explores the possible intrinsic epigenetic molecular mechanisms underlying the heterogeneity of hepatocellular carcinoma.

Retrospective study of the differences of biomarker expression between primary lesions of breast cancer and corresponding lymph node metastases / 国际外科学杂志

Objective To investigate the difference of the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein between primary lesions of breast cancer and its synchronous ipsilateral lymph node metastasis,as well as its clinical implications.Methods Retrospectively analyze invasive breast cancer patients treated in Peking University First Hospital from January 2012 to May 2016.The IHC expressions of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein in both the primary and lymph node metastatic lesions are compared and analyzed statistically.The count data were represented as n(％),and comparsion between groups were evaluated using the McNemar test.Results One hundred and fifty-six patients were included,of which on 2 cases (1.3％),estrogen receptor status of primary lesions is different from that of lymph node metastases(P =0.500);on 10 cases (6.4％),progesterone receptor status of primary lesions is different from that of lymph node metastases (P =0.344);on 28 cases (18.0％),Ki-67 protein status of primary lesions is different from that of lymph node metastases (P =0.000 18);on 3 cases (1.9％),human epidermal growth factor receptor 2 status of primary lesions is different from that of lymph node metastases (P =1.000).Conclusion There may be difference between primary lesions and lymph node metastases in the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein,which can provide a reference for individualized treatment of breast cancer patients.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease / 中华医学杂志(英文版)

<p><b>Background</b>Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations.</p><p><b>Methods</b>Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted.</p><p><b>Results</b>Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones (c.796C>A, c.1057C>T, c.1201C>A, c.1780C>T, c.1799G>C, c.2051C>A, c.2235dupG), were identified by genetic tests.</p><p><b>Conclusions</b>The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.</p>

The Clinical and Molecular Characteristics of Adenocarcinoma Presented by Multi-focal GGO / 中国肺癌杂志

Due to emphasis on early screening for lung cancer, the detection rate of multiple ground glass opacities (GGOs) on computed tomography (CT) image increases in recent years, and research on multifocal adenocarcinomas presented by GGOs has been thriving. It is more common in women and non-smokers and has excellent prognosis both in patients with natural history and after surgery. These clinical features suggest that it is likely to be a distinct disease entity. From the perspective of molecular genetics, lesions in the same individual are likely to have distinct clonal features. Therefore, genetic heterogeneity is the most prominent feature of multifocal pulmonary adenocarcinomas with GGOs. The genetic heterogeneity is expected to assist the diagnosis of multifocal pulmonary adenocarcinoma and intrapulmonary metastasis, and also suggests that genetic testing of the GGO lesions is of great therapeutic significance. Some GGO lesions may harvest the similar clonal feature, which provide new evidence for the theory of spread through air spaces (STAS).
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Familial progressive hyper- and hypopigmentation: a report on a Chinese family and evidence for genetic heterogeneity

Abstract Background: Familial progressive hyper- and hypopigmentation (FPHH) is a rare genodermatosis that is characterized by diffuse hyper- and hypopigmented spots on the skin and mucous membranes. It is caused by a pathogenic mutation of the KITLG gene. Objectives: To investigate the clinical features and mutation of the KITLG gene in a Chinese family with FPHH. Methods: Histopathological and immunohistochemical analysis of lesions from the proband was performed. The KITLG gene was screened for the presence of mutations. Results: A Chinese family containing 14 individuals with FPHH was described, and the proband was a 5-year-old girl showing diffuse hyper- and hypopigmented lesions on her extremities and trunk. Histopathological and immunohistochemical staining for S100 and HMB45 of skin biopsy specimens from the hyperpigmented areas showed a striking increase in melanin throughout the epidermis, especially in the basal cell layer, and staining of hypopigmented area specimens displayed lower levels of melanin in the epidermis. Mutation analysis of the KITLG gene was performed, but no mutation was found. Study limitations: The new pathogenic gene was not found. Conclusion: A family with FPHH was described. Analysis revealed that its members did not have any mutations of the KITLG gene, which provided evidence for genetic heterogeneity of this genodermatosis.

Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGMTM Platform / 法医学杂志

Objective To analyze and detect the whole genome sequence of human mitochondrial DNA (mtDNA) by Ion Torrent PGMTM platform and to study the differences of mtDNA sequence in different tissues.Methods Samples were collected from 6 unrelated individuals by forensic postmortem examination,including chest blood,hair,costicartilage,nail,skeletal muscle and oral epithelium.Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer.Libraries were constructed with Ion ShearTM Plus Reagents kit and Ion Plus Fragment Library kit.Whole genome sequencing of mtDNA was performed using Ion Torrent PGMTM platform.Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HV Ⅰ region.Results The whole genome sequence of mtDNA from all samples were amplified successfully.Six unrelated individuals belonged to 6 different haplotypes.Different tissues in one individual had heteroplasmy difference.The heteroplasmy positions and the mutation positions on HV I region were verified by Sanger sequencing.After a consistency check by the Kappa method,it was found that the results of mtDNA sequence had a high consistency in different tissues.Conclusion The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues,which have good consistency.The results provide guidance for the further applications of mtDNA in forensic science.

Advance in genetic study of pituitary stalk interruption syndrome / 中华内分泌代谢杂志

Pituitary stalk interruption syndrome(PSIS) is a developmental defect,characterized by a thin or absent pituitary stalk. PSIS is a rare disease with combined pituitary hormone deficiencies, the pathogenesis of which is related to genetic mutations and environmental factors. It is also a genetically and clinically heterogeneous disease. Nine genes were found to be related to PSIS,including HESX1,LHX4,OTX2,SOX3,CDON,GPR161, PROKR2,TGIF and Wnt,Notch,SHH signalling pathways. In recent years,the intensive genetic studies show that four novel genes(CDON,GPR161,PROKR2,TGIF)and SHH pathway are related to PSIS,which provides a brand-new etiopathogenesis of PSIS.

Clinical application of tumor heterogeneity based on MRI texture analysis / 国际肿瘤学杂志

Heterogeneity is one of the important features of malignant tumors.MRI texture analysis (MTA) is a new imaging post-processing technique to quantify heterogeneity of tumor.Increasing number of studies have shown that MTA is a potentially useful tool in tumor imaging,and can provide important and valuable information including tumor characteristics,prognosis assessment,prediction or monitoring of tumor treatment response,and so on.In this article,we review the literatures about MTA in evaluating heterogeneity of tumor.The correlation between MTA and tumor response to chemotherapy,prognosis and survival time,and the role of MTA as imaging markers in clinical practice are summarized,to further explore its potential in clinical application.

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.