Journal of translational genetics and genomics最新文献_第10页

Adenoid cystic carcinoma of the prostate: an unusual subtype of prostate cancer 前列腺腺样囊性癌:前列腺癌的一种罕见亚型

Journal of translational genetics and genomics Pub Date : 2020-01-01 DOI: 10.20517/jtgg.2020.46

P. Julka

{"title":"Adenoid cystic carcinoma of the prostate: an unusual subtype of prostate cancer","authors":"P. Julka","doi":"10.20517/jtgg.2020.46","DOIUrl":"https://doi.org/10.20517/jtgg.2020.46","url":null,"abstract":"Adenoid cystic carcinoma (ACC) of the prostate is an extremely rare disease that arises from the basal cells of prostate acini and presents a poor prognosis for metastatic cases. Multiple treatment options exist for different stages of prostate cancer that include prostatectomy, radiation therapy, chemotherapy, and hormone therapy with gonadrotropin-releasing hormone (GnRH) agonists and antagonists for androgen receptor (AR)-positive cases. Although ACC has a biological potential that allows metastasis in a few cases; the current treatment option consists primarily of surgical resection along with close, long-term follow-up. Herein, we report this rare entity in a 79-year-old man who presented with liver metastasis. The tumor expressed GnRH receptor (GnRHR) and a very low level of Programmed death-ligand 1 (PD-L1). Immunohistochemical analysis revealed that the primary tumor was highly proliferative and AR-negative. We employed a clinically validated technology that utilizes patient's tumor and blood to recreate the tumor microenvironment ex vivo . After the diagnosis, we used the platform to test the efficacy of degarelix (a GnRHR antagonist), atezolizumab (a PD-L1 antagonist) and paclitaxel + carboplatin chemotherapeutic regimen. The assay output predicted response with chemotherapeutics and degarelix, without any sign of efficacy for PD-L1 antagonist. On the basis of these data, the patient was treated with paclitaxel + carboplatin combination chemotherapy first and showed clinical and radiological response as predicted by the ex vivo platform. After 4 cycles of chemotherapy, the patient received maintenance therapy with degarelix and demonstrated a favorable clinical response. Taken together, our results not only showed the accurate prediction Page 456 Julka et al. J Transl Genet Genom 2020;4:455-63 I http://dx.doi.org/10.20517/jtgg.2020.46 of clinical outcome but also demonstrate the rational selection of a regimen as a viable option for such a clinically challenging disease.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Mitochondrial diseases: expanding the diagnosis in the era of genetic testing. 线粒体疾病:在基因检测时代扩大诊断。

Journal of translational genetics and genomics Pub Date : 2020-01-01 Epub Date: 2020-09-29 DOI: 10.20517/jtgg.2020.40

Russell P Saneto

{"title":"Mitochondrial diseases: expanding the diagnosis in the era of genetic testing.","authors":"Russell P Saneto","doi":"10.20517/jtgg.2020.40","DOIUrl":"10.20517/jtgg.2020.40","url":null,"abstract":"Mitochondrial diseases are clinically and genetically heterogeneous. These diseases were initially described a little over three decades ago. Limited diagnostic tools created disease descriptions based on clinical, biochemical analytes, neuroimaging, and muscle biopsy findings. This diagnostic mechanism continued to evolve detection of inherited oxidative phosphorylation disorders and expanded discovery of mitochondrial physiology over the next two decades. Limited genetic testing hampered the definitive diagnostic identification and breadth of diseases. Over the last decade, the development and incorporation of massive parallel sequencing has identified approximately 300 genes involved in mitochondrial disease. Gene testing has enlarged our understanding of how genetic defects lead to cellular dysfunction and disease. These findings have expanded the understanding of how mechanisms of mitochondrial physiology can induce dysfunction and disease, but the complete collection of disease-causing gene variants remains incomplete. This article reviews the developments in disease gene discovery and the incorporation of gene findings with mitochondrial physiology. This understanding is critical to the development of targeted therapies.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38804217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Redefining infantile-onset multisystem phenotypes of coenzyme Q₁₀-deficiency in the next-generation sequencing era. 在下一代测序时代重新定义辅酶q10缺乏症的婴儿发病多系统表型。

Journal of translational genetics and genomics Pub Date : 2020-01-01 Epub Date: 2020-04-23 DOI: 10.20517/jtgg.2020.02

Andres Berardo, Catarina M Quinzii

{"title":"Redefining infantile-onset multisystem phenotypes of coenzyme Q10-deficiency in the next-generation sequencing era.","authors":"Andres Berardo, Catarina M Quinzii","doi":"10.20517/jtgg.2020.02","DOIUrl":"https://doi.org/10.20517/jtgg.2020.02","url":null,"abstract":"Primary coenzyme Q10 (CoQ10) deficiency encompasses a subset of mitochondrial diseases caused by mutations affecting proteins involved in the CoQ10 biosynthetic pathway. One of the most frequent clinical syndromes associated with primary CoQ10 deficiency is the severe infantile multisystemic form, which, until recently, was underdiagnosed. In the last few years, the availability of genetic screening through whole exome sequencing and whole genome sequencing has enabled molecular diagnosis in a growing number of patients with this syndrome and has revealed new disease phenotypes and molecular defects in CoQ10 biosynthetic pathway genes. Early genetic screening can rapidly and non-invasively diagnose primary CoQ10 deficiencies. Early diagnosis is particularly important in cases of CoQ10 deficient steroid-resistant nephrotic syndrome, which frequently improves with treatment. In contrast, the infantile multisystemic forms of CoQ10 deficiency, particularly when manifesting with encephalopathy, present therapeutic challenges, due to poor responses to CoQ10 supplementation. Administration of CoQ10 biosynthetic intermediate compounds is a promising alternative to CoQ10; however, further pre-clinical studies are needed to establish their safety and efficacy, as well as to elucidate the mechanism of actions of the intermediates. Here, we review the molecular defects causes of the multisystemic infantile phenotype of primary CoQ10 deficiency, genotype-phenotype correlations, and recent therapeutic advances.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38804212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Mitochondrial translation defects and human disease. 线粒体翻译缺陷与人类疾病。

Journal of translational genetics and genomics Pub Date : 2020-01-01 Epub Date: 2020-05-23 DOI: 10.20517/jtgg.2020.11

Bryn D Webb, George A Diaz, Pankaj Prasun

引用次数: 13

Towards clinical implementation of circulating cell-free DNA in precision medicine. 循环无细胞DNA在精准医学中的临床应用。

Journal of translational genetics and genomics Pub Date : 2019-09-01 DOI: 10.20517/jtgg.2019.07

Wei Zhang

引用次数: 2

microRNAs in asthma pathogenesis - from mouse to man microrna在哮喘发病机制中的作用——从小鼠到人类

Journal of translational genetics and genomics Pub Date : 2019-01-20 DOI: 10.20517/JTGG.2018.30

J. Weidner, C. Malmhäll, M. Rådinger

引用次数: 16

Evolution of the prostate cancer genome towards resistance 前列腺癌基因组向耐药性的进化

Journal of translational genetics and genomics Pub Date : 2019-01-01 DOI: 10.20517/JTGG.2019.01

F. Lorenzin, F. Demichelis

{"title":"Evolution of the prostate cancer genome towards resistance","authors":"F. Lorenzin, F. Demichelis","doi":"10.20517/JTGG.2019.01","DOIUrl":"https://doi.org/10.20517/JTGG.2019.01","url":null,"abstract":"The clinical behavior of prostate cancer is highly heterogeneous, with most patients diagnosed with localized disease that successfully responds to surgery or radiotherapy or that can be followed by active surveillance. However, a fraction of men will relapse after initial treatment and eventually progress to an aggressive resistant form with metastasis spreading and high mortality, a state referred to as castration resistant prostate cancer (CRPC). The technological advances in next generation sequencing have enabled the deep genomic and epigenomic characterization of both the hormone naïve and CRPC states, leading to the definition of molecular subclasses of prostate cancer that could inform the clinicians on therapeutic strategies. These studies also shed light on the mechanisms driving resistance to therapy. CRPCs adapt to androgen receptor (AR) signaling impairment which follows first-line therapies as androgen deprivation or AR targeting by restoring the nuclear receptor signaling by means of multiple mechanisms. Alternatively, tumor cells might become resistant to targeted therapies by exploiting lineage plasticity and activating alternative pathways. This review will discuss the main mechanisms leading to the emergence of resistance to therapy in prostate cancer patients in the context of genomic and molecular features of CRPC and on their causal role in the development of resistance.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73433512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Genomic biomarkers for chronic kidney disease: the first step towards personalized medicine? 慢性肾脏疾病的基因组生物标志物:迈向个体化医疗的第一步?

Journal of translational genetics and genomics Pub Date : 2019-01-01 DOI: 10.20517/jtgg.2018.16

Jingyuan Cao, Le-ting Zhou, Bi-Cheng Liu

{"title":"Genomic biomarkers for chronic kidney disease: the first step towards personalized medicine?","authors":"Jingyuan Cao, Le-ting Zhou, Bi-Cheng Liu","doi":"10.20517/jtgg.2018.16","DOIUrl":"https://doi.org/10.20517/jtgg.2018.16","url":null,"abstract":"With the prevalence of end stage renal disease steadily increasing, chronic kidney disease (CKD) represents an impending public healthcare challenge. Classical diagnostic biomarkers of CKD, including creatinine, have low sensitivity and specificity. Thus, novel diagnostic and prognostic biomarkers for patients at high risk of early-stage progression are urgently needed. Personalized medicine approaches generally stratify patients according to their biological or genomic make-up. Targeted clinical trials require more precise identification of these subgroups. The use of new biomarkers obtained via high-throughput technologies is expected in future, accompanied by vast improvements in computational power applied in genomics, proteomics, and metabolomics studies using biological fluids and renal biopsy tissue. Genomic biomarkers may not only provide additional information regarding the etiology and mechanisms underlying CKD progression, but may also enable early diagnosis and the selection of appropriate drugs, thereby personalizing therapy. This review discusses commonly used research methods in genomic medicine and summarizes currently available genomic biomarkers in inherited and acquired CKD.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67658288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overview of liposarcomas and their genomic landscape 脂肪肉瘤的概述及其基因组景观

Journal of translational genetics and genomics Pub Date : 2019-01-01 DOI: 10.20517/JTGG.2019.03

E. Keung, N. Somaiah

引用次数: 14

Emerging role of MicroRNAs in allergic diseases microrna在过敏性疾病中的新作用

Journal of translational genetics and genomics Pub Date : 2019-01-01 DOI: 10.20517/jtgg.2018.32

F. Ishmael

引用次数: 0