Chemoresistant pleomorphic rhabdomyosarcoma: whole exome sequencing reveals underlying cancer predisposition and therapeutic options

2018 ◽  
Vol 57 (2) ◽  
pp. 104-108 ◽  
Author(s):  
Camille Tlemsani ◽  
Karen Leroy ◽  
Anne-Paule Gimenez-Roqueplo ◽  
Audrey Mansuet-Lupo ◽  
Eric Pasmant ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Lung Metastases ◽  
Genomic Medicine ◽  
Treatment Decision ◽  
Complete Response ◽  
Tumour Cells ◽  
Therapeutic Options ◽  
Whole Exome

BackgroundRhabdomyosarcoma (RMS) is rare cancer affecting children and adults. Pleomorphic RMS histology is almost exclusive to adult patients and often resistant to chemotherapy.ObjectiveWe report the case of a 19-year-old patient who presented with a metastatic chemoresistant pleomorphic RMS.MethodsConsidering the poor prognosis and the few systemic therapeutic options, we decided to carry out a whole exome sequencing (WES) of the tumour and germline DNA.ResultsWES identified a germline variation (c.1863_1864insT) in the MLH1 gene corresponding to a pathogenic mutation: (p. Leu622Serfs*10), whereas the family history did not fit with classical criteria for Lynch syndrome. Loss-of-heterozygosity at MLH1 locus was found in the tumour. Immunohistochemistry showed loss of MLH1 and PMS2 nuclear expression in the tumour cells. In view of the mismatch repair defects and a high programmed cell death ligand 1 (PD-L1) expression (60% of tumour cells expressed PD-L1), we administrated an anti-PD-1 antibody to the patient. He achieved a rapid complete response of the lung metastases, which appears sustained after a 1-year follow-up.ConclusionThis observation of an RMS revealing an unexpected Lynch syndrome underlines the overlap between tumorous and germline molecular genetics and emphasises the major impact of cancer genomic medicine in clinical practice for guiding treatment decision.

scholarly journals Lynch Syndrome Patients’ Views of and Preferences for Return of Results Following Whole Exome Sequencing

2014 ◽  
Vol 23 (4) ◽  
pp. 539-551 ◽  
Author(s):  
Kelly Hitch ◽  
Galen Joseph ◽  
Jenna Guiltinan ◽  
Jessica Kianmahd ◽  
Janey Youngblom ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Return Of Results ◽  
Whole Exome

scholarly journals The use of PanDrugs to prioritize anticancer drug treatments in a case of T-ALL based on individual genomic data

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Pablo Fernández-Navarro ◽  
Pilar López-Nieva ◽  
Elena Piñeiro-Yañez ◽  
Gonzalo Carreño-Tarragona ◽  
Joaquín Martinez-López ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Lymphoblastic Leukaemia ◽  
Large Scale ◽  
Genomic Medicine ◽  
Fusion Transcript ◽  
Sequencing Technologies ◽  
Dna And Rna ◽  
Whole Exome ◽  
New Treatment

Abstract Background Acute T-cell lymphoblastic leukaemia (T-ALL) is an aggressive disorder derived from immature thymocytes. The variability observed in clinical responses on this type of tumours to treatments, the high toxicity of current protocols and the poor prognosis of patients with relapse or refractory make it urgent to find less toxic and more effective therapies in the context of a personalized medicine of precision. Methods Whole exome sequencing and RNAseq were performed on DNA and RNA respectively, extracted of a bone marrow sample from a patient diagnosed with tumour primary T-ALL and double negative thymocytes from thymus control samples. We used PanDrugs, a computational resource to propose pharmacological therapies based on our experimental results, including lists of variants and genes. We extend the possible therapeutic options for the patient by taking into account multiple genomic events potentially sensitive to a treatment, the context of the pathway and the pharmacological evidence already known by large-scale experiments. Results As a proof-of-principle we used next-generation-sequencing technologies (Whole Exome Sequencing and RNA-Sequencing) in a case of diagnosed Pro-T acute lymphoblastic leukaemia. We identified 689 disease-causing mutations involving 308 genes, as well as multiple fusion transcript variants, alternative splicing, and 6652 genes with at least one principal isoform significantly deregulated. Only 12 genes, with 27 pathogenic gene variants, were among the most frequently mutated ones in this type of lymphoproliferative disorder. Among them, 5 variants detected in CTCF, FBXW7, JAK1, NOTCH1 and WT1 genes have not yet been reported in T-ALL pathogenesis. Conclusions Personalized genomic medicine is a therapeutic approach involving the use of an individual’s information data to tailor drug therapy. Implementing bioinformatics platform PanDrugs enables us to propose a prioritized list of anticancer drugs as the best theoretical therapeutic candidates to treat this patient has been the goal of this article. Of note, most of the proposed drugs are not being yet considered in the clinical practice of this type of cancer opening up the approach of new treatment possibilities.

scholarly journals Whole exome sequencing of circulating and disseminated tumour cells in patients with metastatic breast cancer

2015 ◽  
Vol 26 ◽  
pp. iii10
Author(s):  
D. Peeters ◽  
A. Brouwer ◽  
K. Op de Beeck ◽  
G. Van de Weyer ◽  
P. Pauwels ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Metastatic Breast ◽  
Tumour Cells ◽  
Whole Exome ◽  
Disseminated Tumour Cells

scholarly journals Whole Exome Sequencing in 20,197 Persons for Rare Variants in Alzheimer Disease

2018 ◽  
Author(s):  
Neha S. Raghavan ◽  
Adam M. Brickman ◽  
Howard Andrews ◽  
Jennifer J. Manly ◽  
Nicole Schupf ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
Age At Onset ◽  
Genomic Medicine ◽  
Loss Of Function ◽  
Whole Exome ◽  
A Genome

AbstractObjectiveThe genetic bases of Alzheimer’s disease remain uncertain. An international effort to fully articulate genetic risks and protective factors is underway with the hope of identifying potential therapeutic targets and preventive strategies. The goal here was to identify and characterize the frequency and impact of rare and ultra-rare variants in Alzheimer’s disease using whole exome sequencing in 20,197 individuals.MethodsWe used a gene-based collapsing analysis of loss-of-function ultra-rare variants in a case-control study design with data from the Washington Heights-Inwood Columbia Aging Project, the Alzheimer’s Disease Sequencing Project and unrelated individuals from the Institute of Genomic Medicine at Columbia University.ResultsWe identified 19 cases carrying extremely rare SORL1 loss-of-function variants among a collection of 6,965 cases and a single loss-of-function variant among 13,252 controls (p = 2.17 × 10-8; OR 36.2 [95%CI 5.8 – 1493.0]). Age-at-onset was seven years earlier for patients with SORL1 qualifying variant compared with non-carriers. No other gene attained a study-wide level of statistical significance, but multiple top-ranked genes, including GRID2IP, WDR76 and GRN, were among candidates for follow-up studies.InterpretationThis study implicates ultra-rare, loss-of-function variants in SORL1 as a significant genetic risk factor for Alzheimer’s disease and provides a comprehensive dataset comparing the burden of rare variation in nearly all human genes in Alzheimer’s disease cases and controls. This is the first investigation to establish a genome-wide statistically significant association between multiple extremely rare loss-of-function variants in SORL1 and Alzheimer’s disease in a large whole-exome study of unrelated cases and controls.

scholarly journals Gene big data- A Research for Monogenic Hypertension Diagnosis

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Kuangyi Wei
Keyword(s):  
Big Data ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Therapeutic Option ◽  
Point Mutations ◽  
Therapeutic Options ◽  
Detailed Procedure ◽  
Whole Exome ◽  
Hypertension Diagnosis ◽  
Monogenic Hypertension

This paper designed a detailed procedure for monogenic hypertension diagnosis by Whole Exome Sequencing (WES) and provided reliable precise medication guidance. Identification of mutated points provides the clinician valuable information for effective individualized therapeutic option. Therapeutic options that specifically restore the pathway disturbed by these point mutations can be selected to give a precise medicinal guidance.  

scholarly journals Whole-exome sequencing identified a novel mutation of MLH1 in an extended family with lynch syndrome

2020 ◽  
Vol 7 (4) ◽  
pp. 614-619
Author(s):  
Hamid Ghaedi ◽  
Samira Molaei Ramsheh ◽  
Maryam Erfanian Omidvar ◽  
Afsaneh Labbaf ◽  
Elham Alehabib ◽  
...  
Keyword(s):  
Lynch Syndrome ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Extended Family ◽  
Novel Mutation ◽  
Whole Exome
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