Multiregion Whole-Exome Sequencing Uncovers the Genetic Evolution and Mutational Heterogeneity of Early-Stage Metastatic Melanoma

Background. Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related mortality in China with increasing incidence. This study is designed to explore early genetic changes implicated in HCC tumorigenesis and progression by whole-exome sequencing. Methods. We firstly sequenced the whole exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood samples, followed by gene ontological analysis and pathway analysis of the single-nucleotide variants discovered. Then, the mutations of high frequency were further confirmed by Sanger sequencing. Results. We identified a mutational signature of dominant T:A>A:T transversion in early HCC and significantly enriched pathways including ECM-receptor interaction, axon guidance, and focal adhesion and enriched biological processes containing cell adhesion, axon guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A, DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions. This study reveals a mutational profile and a distinct mutation signature of T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our understanding of genetic characteristics of the early-stage HCC.

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Whole-exome sequencing and clonal evolution of brain metastases in low-grade early-stage endometroid endometrial adenocarcinoma

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.05.369 ◽

2020 ◽

Vol 159 ◽

pp. 222-223

Author(s):

K. Dessources ◽

A.D.C. Paula ◽

P. Cybulska ◽

F. Pareja ◽

A. Stylianou ◽

...

Keyword(s):

Brain Metastases ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Stage ◽

Clonal Evolution ◽

Endometrial Adenocarcinoma ◽

Low Grade ◽

Whole Exome

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Clinical significance of circulating tumor cells via combined whole exome sequencing in early stage cancer screening: A case report

Experimental and Therapeutic Medicine ◽

10.3892/etm.2018.6507 ◽

2018 ◽

Cited By ~ 2

Author(s):

Zijian Su ◽

Jiangman Zhao ◽

Shaoying Ke ◽

Jian Zhang ◽

Xiaoyu Liu ◽

...

Keyword(s):

Case Report ◽

Cancer Screening ◽

Exome Sequencing ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Whole Exome Sequencing ◽

Clinical Significance ◽

Early Stage ◽

Early Stage Cancer ◽

Whole Exome

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Abstract 89: Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma

10.1158/1538-7445.am2016-89 ◽

2016 ◽

Author(s):

Humam Kadara ◽

Murim Choi ◽

Jiexin Zhang ◽

Edwin Parra Cuentas ◽

Jaime Rodriguez Canales ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Stage ◽

Whole Exome ◽

Immune Profiling

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Analysis of the Whole-Exome Sequencing of Tumor and Circulating Tumor DNA in Metastatic Melanoma

Cancers ◽

10.3390/cancers11121905 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1905

Author(s):

Russell J. Diefenbach ◽

Jenny H. Lee ◽

Dario Strbenac ◽

Jean Y. H. Yang ◽

Alexander M. Menzies ◽

...

Keyword(s):

Metastatic Melanoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Cancer Progression ◽

Low Frequency ◽

Circulating Tumor Dna ◽

Response To Therapy ◽

Driver Mutations ◽

Whole Exome ◽

Tumor Dna

The use of circulating tumor DNA (ctDNA) to monitor cancer progression and response to therapy has significant potential but there is only limited data on whether this technique can detect the presence of low frequency subclones that may ultimately confer therapy resistance. In this study, we sought to evaluate whether whole-exome sequencing (WES) of ctDNA could accurately profile the mutation landscape of metastatic melanoma. We used WES to identify variants in matched, tumor-derived genomic DNA (gDNA) and plasma-derived ctDNA isolated from a cohort of 10 metastatic cutaneous melanoma patients. WES parameters such as sequencing coverage and total sequencing reads were comparable between gDNA and ctDNA. The mutant allele frequency of common single nucleotide variants was lower in ctDNA, reflecting the lower read depth and minor fraction of ctDNA within the total circulating free DNA pool. There was also variable concordance between gDNA and ctDNA based on the total number and identity of detected variants and this was independent of the tumor biopsy site. Nevertheless, established melanoma driver mutations and several other melanoma-associated mutations were concordant between matched gDNA and ctDNA. This study highlights that WES of ctDNA could capture clinically relevant mutations present in melanoma metastases and that enhanced sequencing sensitivity will be required to identify low frequency mutations.

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Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up

Annals of Oncology ◽

10.1093/annonc/mdw436 ◽

2017 ◽

Vol 28 (1) ◽

pp. 75-82 ◽

Cited By ~ 58

Author(s):

H Kadara ◽

M Choi ◽

J. Zhang ◽

E.R. Parra ◽

J. Rodriguez-Canales ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Stage ◽

Whole Exome ◽

Immune Profiling

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Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up

Annals of Oncology ◽

10.1093/annonc/mdx062 ◽

2018 ◽

Vol 29 (4) ◽

pp. 1072 ◽

Cited By ~ 7

Author(s):

H. Kadara ◽

M. Choi ◽

J. Zhang ◽

E.R. Parra ◽

J. Rodriguez-Canales ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Stage ◽

Whole Exome ◽

Immune Profiling

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Whole Exome Sequencing-Based Identification of a Novel Gene Involved in Root Hair Development in Barley (Hordeum vulgare L.)

International Journal of Molecular Sciences ◽

10.3390/ijms222413411 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13411

Author(s):

Katarzyna Gajek ◽

Agnieszka Janiak ◽

Urszula Korotko ◽

Beata Chmielewska ◽

Marek Marzec ◽

...

Keyword(s):

Hordeum Vulgare ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Root Hair ◽

Early Stage ◽

Root Hairs ◽

Chemical Mutagenesis ◽

Hordeum Vulgare L ◽

Root Hair Development ◽

Whole Exome

Root hairs play a crucial role in anchoring plants in soil, interaction with microorganisms and nutrient uptake from the rhizosphere. In contrast to Arabidopsis, there is a limited knowledge of root hair morphogenesis in monocots, including barley (Hordeum vulgare L.). We have isolated barley mutant rhp1.e with an abnormal root hair phenotype after chemical mutagenesis of spring cultivar ‘Sebastian’. The development of root hairs was initiated in the mutant but inhibited at the very early stage of tip growth. The length of root hairs reached only 3% of the length of parent cultivar. Using a whole exome sequencing (WES) approach, we identified G1674A mutation in the HORVU1Hr1G077230 gene, located on chromosome 1HL and encoding a cellulose synthase-like C1 protein (HvCSLC1) that might be involved in the xyloglucan (XyG) synthesis in root hairs. The identified mutation led to the retention of the second intron and premature termination of the HvCSLC1 protein. The mutation co-segregated with the abnormal root hair phenotype in the F2 progeny of rhp1.e mutant and its wild-type parent. Additionally, different substitutions in HORVU1Hr1G077230 were found in four other allelic mutants with the same root hair phenotype. Here, we discuss the putative role of HvCSLC1 protein in root hair tube elongation in barley.

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