scholarly journals Identification of a novel somatic mutation of POU6F2 by whole‐genome sequencing in prolactinoma

2019 ◽  
Vol 7 (12) ◽  
Author(s):  
Yazhou Miao ◽  
Chuzhong Li ◽  
Jing Guo ◽  
Hongyun Wang ◽  
Lei Gong ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mutation ◽  
Whole Genome

scholarly journals A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Tyler S. Alioto ◽  
Ivo Buchhalter ◽  
Sophia Derdak ◽  
Barbara Hutter ◽  
Matthew D. Eldridge ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mutation ◽  
Mutation Detection ◽  
Comprehensive Assessment ◽  
Whole Genome ◽  
Somatic Mutation Detection

Whole Genome Sequence Analysis of Primary Myelofibrosis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2863-2863
Author(s):  
Jason D. Merker ◽  
Krishna Roskin ◽  
Dana Ng ◽  
Cuiping Pan ◽  
Dianna G. Fisk ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mutation ◽  
Somatic Mutations ◽  
Jak2 V617f ◽  
Skin Fibroblasts ◽  
Additional Patient ◽  
Whole Genome ◽  
Cultured Skin ◽  
Recurrent Mutations

Abstract Abstract 2863 Background: JAK2 V617F is a recurrent, activating mutation in patients (pts) with BCR-ABL1-negative MPNs. Mutations in codon 515 of MPL occur in 1–5% and 5–10% of ET and PMF pts, respectively, and similar to JAK2 V617F, lead to constitutive JAK-STAT signaling. The acquisition of multiple mutational events affecting the JAK-STAT axis or components of the epigenetic machinery is common in MPNs and likely contributes to phenotypic diversity, including progression to acute myeloid leukemia. Mutated genes thus far implicated in MPN initiation and/or progression include TET2, CBL, SH2B3, ASXL1, DNMT3A, IDH1/2, IKZF1, EZH2, SRSF2, and TP53. In order to identify novel somatic mutations associated with classic BCR-ABL1-negative MPNs, we performed whole genome sequencing of DNA extracted from peripheral blood granulocytes and cultured skin fibroblasts from a patient with PMF and a known MPL W515K mutation. Methods: Whole genome sequencing (WGS) was undertaken in a 55 year-old man with untreated PMF four years after initial diagnosis. His DIPSS Plus risk group was low (score 0). His karyotype was normal, and molecular testing revealed wild-type JAK2 in addition to the MPL W515K mutation. WGS of purified granulocytes and paired cultured skin fibroblasts was performed using both Illumina HiSeq and Complete Genomics (CGI) platforms. The resulting data were analyzed using multiple independent aligners and variant callers. Amplicon-based targeted resequencing with the Illumina MiSeq platform was used to evaluate additional patient samples for recurrent mutations. Stanford institutional review board approval and informed pt consent was obtained for these analyses. Results: The PMF genome was sequenced to 88X (Illumina) and 128X (CGI) average fold coverage, and the cultured skin fibroblast genome was sequenced to 47X (Illumina) and 126X (CGI). The PMF genome had a low somatic mutation rate, consistent with that observed for other sequenced hematopoietic tumor genomes, with a low number of true somatic mutation calls. To definitively identify true mutations among various sequencing artefacts and germline variants, we use cultured skin fibroblasts which can be prepared with no contamination by neoplastic cells. In addition to re-identification of the MPL W515K mutation, this approach identified six additional somatic mutations that alter gene coding regions, splice sites, or known regulatory regions: a nonsense mutation in CARD6, implicated in modulation of NF-kappaB activation; a splice-site mutation in CAP2; three nonsynonymous point mutations in KIAA0355, SOX30, MFRP; and a 19-base pair (bp) deletion involving a regulatory region in the 5'-untranslated region (5'-UTR) of BRD2, a bromodomain-containing protein implicated in transcriptional regulation (Table). CARD6, BRD2, and KIAA0355, an uncharacterized protein, are expressed by the granulocytes derived from this patient, supporting a potential role in the development of PMF in this pt. Using massively parallel sequencing, we are currently examining the transcribed region of BRD2 and the coding region of the other five genes in additional pt samples. Analysis of the first 87 samples (MF=47, PV=20, ET=20) out of a cohort of 180 MPN pts has thus far not identified recurrent somatic mutations in these six genes. Conclusion: High-coverage genome sequencing of neoplastic and germline cells from a patient with MPL-mutated PMF identified six additional somatic mutations of potential functional significance. Work is ongoing to determine if somatic mutations in these genes are found in other patients with BCR-ABL1-negative MPNs, and their pathogenetic relevance to MPN biology. Disclosures: Snyder: Illumina: Consultancy; GenapSys: Membership on an entity's Board of Directors or advisory committees; Personalis: Consultancy, Founder Other.

scholarly journals Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly

Blood ◽  
2017 ◽  
Vol 130 (6) ◽  
pp. 742-752 ◽  
Author(s):  
Florian Zink ◽  
Simon N. Stacey ◽  
Gudmundur L. Norddahl ◽  
Michael L. Frigge ◽  
Olafur T. Magnusson ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Somatic Mutation ◽  
The Elderly ◽  
Driver Mutations ◽  
Whole Genome ◽  
Clonal Hematopoiesis ◽  
Key Points

Key Points Whole-genome sequencing of 11 262 Icelanders reveals that clonal hematopoiesis is very common in the elderly. Somatic mutation of some genes is strongly associated with clonal hematopoiesis, but in most cases, no driver mutations were evident.

Utility of Whole Genome Sequencing in diagnosing complex disorders: lesson from renal tubular disorders

2018 ◽  
Author(s):  
Mark Stevenson ◽  
Alistair T Pagnamenta ◽  
Heather G Mack ◽  
Judith A Savige ◽  
Kate E Lines ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Complex Disorders ◽  
Tubular Disorders ◽  
Renal Tubular Disorders ◽  
Renal Tubular
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