scholarly journals Exome sequencing reveals novel oncogenic mutations in early-onset sporadic rectal cancer

2017 ◽  
Vol 1 (Special Issue) ◽  
pp. 58-58
Author(s):  
Pratyusha Bala ◽  
Ravi Gupta ◽  
Murali D. Bashyam
Keyword(s):  
Rectal Cancer ◽  
Exome Sequencing ◽  
Early Onset ◽  
Oncogenic Mutations ◽  
Sporadic Rectal Cancer

scholarly journals Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer

2020 ◽  
Author(s):  
Pratyusha Bala ◽  
Anurag Kumar Singh ◽  
Padmavathi Kavadipula ◽  
Viswakalyan Kotapalli ◽  
Radhakrishnan Sabarinathan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Early Onset ◽  
Target Genes ◽  
Ectopic Expression ◽  
Tumor Formation ◽  
Inhibition Of Growth ◽  
Sporadic Rectal Cancer ◽  
And Migration

AbstractEarly-onset sporadic rectal cancer (EOSRC) is a unique and predominant colorectal cancer (CRC) subtype in India. In order to understand the tumorigenic process in EOSRC, we performed whole exome sequencing of 47 microsatellite stable EOSRC samples. Signature 1 was the predominant mutational signature in EOSRC, as previously shown in other CRC exome studies. More importantly, we identified TP53, KRAS, APC, PIK3R1 and SMAD4 as significantly mutated (q<0.1) and ARID1A and ARID2 as near-significantly mutated (restricted hypothesis testing; q<0.1) candidate drivers. Unlike the other candidates, the tumorigenic potential of ARID2, encoding a component of the SWI/SNF chromatin remodeling complex, is largely unexplored in CRC. shRNA mediated ARID2 knockdown performed in two different CRC cell lines resulted in significant alterations in transcript levels of cancer-related target genes. More importantly, ARID2 knockdown promoted several tumorigenic features including cell viability, proliferation, ability to override contact inhibition of growth, and migration besides significantly increasing tumor formation ability in nude mice. The observed gain in tumorigenic features were rescued upon ectopic expression of ARID2. Analyses of the TCGA CRC dataset revealed poorer survival in patients with ARID2 alterations. We therefore propose ARID2 as a novel tumor suppressor in CRC.

scholarly journals Exome sequencing identifies ARID2 as a novel tumor suppressor in early-onset sporadic rectal cancer

Oncogene ◽  
2020 ◽  
Author(s):  
Pratyusha Bala ◽  
Anurag Kumar Singh ◽  
Padmavathi Kavadipula ◽  
Viswakalyan Kotapalli ◽  
Radhakrishnan Sabarinathan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Suppressor ◽  
Exome Sequencing ◽  
Early Onset ◽  
Sporadic Rectal Cancer

Abstract 1198: Presence of non-canonical tumorigenesis pathways in early-onset sporadic rectal cancer.

2013 ◽  
Author(s):  
Ratheesh Raman ◽  
Viswakalyan Kotapalli ◽  
Raju SR Adduri ◽  
Vasantha Kumar Bhaskara ◽  
Swarnalata Gowrishankar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Early Onset ◽  
Sporadic Rectal Cancer

Utility and implications of exome sequencing in early‐onset Parkinson's disease

2018 ◽  
Vol 34 (1) ◽  
pp. 133-137 ◽  
Author(s):  
Joanne Trinh ◽  
Katja Lohmann ◽  
Hauke Baumann ◽  
Alexander Balck ◽  
Max Borsche ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Exome Sequencing ◽  
Early Onset ◽  
Early Onset Parkinson’S Disease

scholarly journals A Novel Homozygous In-Frame Deletion in Complement Factor 3 Underlies Early-Onset Autosomal Recessive Atypical Hemolytic Uremic Syndrome - Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Shirley Pollack ◽  
Israel Eisenstein ◽  
Adi Mory ◽  
Tamar Paperna ◽  
Ayala Ofir ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Exome Sequencing ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Critical Role ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complement Factor ◽  
Complement Components ◽  
Uremic Syndrome ◽  
Close Relatives

Background and ObjectivesAtypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. Hereditary aHUS due to C3 disruption is rare, usually caused by heterozygous activating mutations in the C3 gene, and transmitted as autosomal dominant traits. We studied the molecular basis of early-onset aHUS, associated with an unusual finding of a novel homozygous activating deletion in C3.Design, Setting, Participants, &amp; MeasurementsA male neonate with eculizumab-responsive fulminant aHUS and C3 hypocomplementemia, and six of his healthy close relatives were investigated. Genetic analysis on genomic DNA was performed by exome sequencing of the patient, followed by targeted Sanger sequencing for variant detection in his close relatives. Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother.ResultsExome sequencing revealed a novel homozygous variant in exon 26 of C3 (c.3322_3333del, p.Ile1108_Lys1111del), within the highly conserved thioester-containing domain (TED), fully segregating with the familial disease phenotype, as compatible with autosomal recessive inheritance. Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack complex, while his healthy heterozygous mother showed intermediate levels of C3 consumption.ConclusionsOur findings represent the first description of aHUS secondary to a novel homozygous deletion in C3 with ensuing unbalanced C3 over-activation, highlighting a critical role for the disrupted C3-TED domain in the disease mechanism.

scholarly journals Screening of dementia genes by whole-exome sequencing in early-onset Alzheimer disease: input and lessons

2015 ◽  
Vol 24 (5) ◽  
pp. 710-716 ◽  
Author(s):  
Gaël Nicolas ◽  
David Wallon ◽  
Camille Charbonnier ◽  
Olivier Quenez ◽  
Stéphane Rousseau ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Whole Exome

scholarly journals Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing

2018 ◽  
Vol 9 ◽  
Author(s):  
Mathias Cavaillé ◽  
Flora Ponelle-Chachuat ◽  
Nancy Uhrhammer ◽  
Sandrine Viala ◽  
Mathilde Gay-Bellile ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Early Onset ◽  
Cowden Syndrome ◽  
Atypical Presentation ◽  
Primary Tumors ◽  
Multiple Primary Tumors ◽  
Whole Exome ◽  
Multiple Primary
Sign in / Sign up

Export Citation Format

Share Document