Genomic landscape of metastatic lung adenocarcinomas from large-scale clinical sequencing

Molluscum contagiosum virus (MCV) is the sole member of the Molluscipoxvirus genus and the causative agent of molluscum contagiosum (MC), a common skin disease. Although it is an important and frequent human pathogen, its genetic landscape and evolutionary history remain largely unknown. In this study, ten novel complete MCV genome sequences of the two most common MCV genotypes were determined (five MCV1 and five MCV2 sequences) and analyzed together with all MCV complete genomes previously deposited in freely accessible sequence repositories (four MCV1 and a single MCV2). In comparison to MCV1, a higher degree of nucleotide sequence conservation was observed among MCV2 genomes. Large-scale recombination events were identified in two newly assembled MCV1 genomes and one MCV2 genome. One recombination event was located in a newly identified recombinant region of the viral genome, and all previously described recombinant regions were re-identified in at least one novel MCV genome. MCV genes comprising the identified recombinant segments have been previously associated with viral interference with host T-cell and NK-cell immune responses. In conclusion, the two most common MCV genotypes emerged along divergent evolutionary pathways from a common ancestor, and the differences in the heterogeneity of MCV1 and MCV2 populations may be attributed to the strictness of the constraints imposed by the host immune response.

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Chronic Myelomonocytic Leukemia—Hematopathology Perspective

Journal of Immunotherapy and Precision Oncology ◽

10.36401/jipo-21-1 ◽

2021 ◽

Author(s):

Siba El Hussein ◽

Sa A. Wang ◽

Naveen Pemmaraju ◽

Joseph D. Khoury ◽

Sanam Loghavi

Keyword(s):

Risk Stratification ◽

Large Scale ◽

Chronic Myelomonocytic Leukemia ◽

Clinical Implications ◽

The Past ◽

Genomic Landscape ◽

Sequencing Studies ◽

Myelomonocytic Leukemia ◽

Insight Into

ABSTRACT Our understanding of chronic myelomonocytic leukemia (CMML) has evolved tremendously over the past decade. Large-scale sequencing studies have led to increased insight into the genomic landscape of CMML and clinical implications of these changes. This in turn has resulted in refined and improved risk stratification models, which to date remain versatile and subject to remodeling, as new and evolving studies continue to refine our understanding of this disease. In this article, we present an up-to-date review of CMML from a hematopathology perspective, while providing a clinically practical summary that sheds light on the constant evolution of our understanding of this disease.

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A phased, diploid assembly of the Cascade hop (Humulus lupulus) genome reveals patterns of selection and haplotype variation

10.1101/786145 ◽

2019 ◽

Cited By ~ 4

Author(s):

Lillian K. Padgitt-Cobb ◽

Sarah B. Kingan ◽

Jackson Wells ◽

Justin Elser ◽

Brent Kronmiller ◽

...

Keyword(s):

Large Scale ◽

Humulus Lupulus ◽

Plant Genome ◽

Repeat Content ◽

Haplotype Variation ◽

Genomic Landscape ◽

Cannabidiolic Acid ◽

Long Read ◽

History Of ◽

Insight Into

AbstractHop (Humulus lupulus L. var Lupulus) is a diploid, dioecious plant with a history of cultivation spanning more than one thousand years. Hop cones are valued for their use in brewing, and around the world, hop has been used in traditional medicine to treat a variety of ailments. Efforts to determine how biochemical pathways responsible for desirable traits are regulated have been challenged by the large, repetitive, and heterozygous genome of hop. We present the first report of a haplotype-phased assembly of a large plant genome. Our assembly and annotation of the Cascade cultivar genome is the most extensive to date. PacBio long-read sequences from hop were assembled with FALCON and phased with FALCON-Unzip. Using the diploid assembly to assess haplotype variation, we discovered genes under positive selection enriched for stress-response, growth, and flowering functions. Comparative analysis of haplotypes provides insight into large-scale structural variation and the selective pressures that have driven hop evolution. Previous studies estimated repeat content at around 60%. With improved resolution of long terminal retrotransposons (LTRs) due to long-read sequencing, we found that hop is nearly 78% repetitive. Our quantification of repeat content provides context for the size of the hop genome, and supports the hypothesis of whole genome duplication (WGD), rather than expansion due to LTRs. With our more complete assembly, we have identified a homolog of cannabidiolic acid synthase (CBDAS) that is expressed in multiple tissues. The approaches we developed to analyze a phased, diploid assembly serve to deepen our understanding of the genomic landscape of hop and may have broader applicability to the study of other large, complex genomes.

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Characterization of the genomic landscape and actionable mutations in Chinese breast cancers by clinical sequencing

Nature Communications ◽

10.1038/s41467-020-19342-3 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Guan-Tian Lang ◽

Yi-Zhou Jiang ◽

Jin-Xiu Shi ◽

Fan Yang ◽

Xiao-Guang Li ◽

...

Keyword(s):

Breast Cancer ◽

Data Exchange ◽

Large Scale ◽

Breast Cancer Subtype ◽

Precision Oncology ◽

Hippo Signaling ◽

Breast Cancers ◽

Loss Of Function ◽

Clinical Tool ◽

Clinical Sequencing

Abstract The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.

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Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer

Cancer Cell ◽

10.1016/j.ccell.2017.12.004 ◽

2018 ◽

Vol 33 (1) ◽

pp. 125-136.e3 ◽

Cited By ~ 188

Author(s):

Rona Yaeger ◽

Walid K. Chatila ◽

Marla D. Lipsyc ◽

Jaclyn F. Hechtman ◽

Andrea Cercek ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Clinical Sequencing ◽

Genomic Landscape

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Harnessing Clinical Sequencing Data for Survival Stratification of Patients With Metastatic Lung Adenocarcinomas

JCO Precision Oncology ◽

10.1200/po.18.00307 ◽

2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Ronglai Shen ◽

Axel Martin ◽

Ai Ni ◽

Matthew Hellmann ◽

Kathryn C. Arbour ◽

...

Keyword(s):

Median Survival ◽

Risk Groups ◽

Routine Care ◽

Sequencing Data ◽

Individual Gene ◽

Public Resource ◽

Metastatic Lung ◽

Patient Prognosis ◽

Lung Adenocarcinomas ◽

Panel Sequencing

PURPOSE Broad-panel sequencing of tumors facilitates routine care of people with cancer as well as clinical trial matching for novel genome-directed therapies. We sought to extend the use of broad-panel sequencing results to survival stratification and clinical outcome prediction. METHODS By using sequencing results from a cohort of 1,054 patients with advanced lung adenocarcinomas, we developed OncoCast, a machine learning tool for survival risk stratification and biomarker identification. RESULTS With OncoCast, we stratified this patient cohort into four risk groups on the basis of tumor genomic profile. Patients whose tumors harbored a high-risk profile had a median survival of 7.3 months (95% CI, 5.5 to 10.9 months) compared with a low-risk group with a median survival of 32.8 months (95% CI, 26.3 to 38.5 months) with a hazard ratio of 4.6 ( P < .001), far superior to any individual gene predictor or standard clinical characteristics. We found that comutations of both STK11 and KEAP1 are strong determinants of unfavorable prognosis with currently available therapies. In patients with targetable oncogenes (eg, EGFR, ALK, ROS1) who received targeted therapies, the tumor genetic background additionally differentiated survival with mutations in TP53 and ARID1A, which contributed to a higher risk score for shorter survival. CONCLUSION A mutational profile derived from broad-panel sequencing presents an effective genomic stratification for patient survival in advanced lung adenocarcinoma. OncoCast is available as a public resource that facilitates the incorporation of mutational data to predict individual patient prognosis and compare risk characteristics of patient populations.

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