Special Issue "Application of Next-Generation Sequencing in Cancers"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: 31 July 2019

Special Issue Editor

Guest Editor
Dr. Vivek Subbiah

Department of Investigational Cancer Therapeutics (A Phase 1 Program), Division of Cancer Medicine, The University of MD Anderson Cancer Center, Houston, TX 77030, USA
Website | E-Mail
Interests: adolescent and young adult oncology; clinical trials with molecularly targeted agents; dramatic responses in cancer patients; N–of-ONE studies; deep sequencing; morphoproteomics; next generation sequencing; Phase 1 trials—drug development (targeted therapy, radiopharmaceutical therapy, and immunotherapy); Basket trials; Rare Oncology histology agnostic trials

Special Issue Information

Dear Colleagues,

Cancer is a genetic disease. With the advent of precision medicine, there has been an explosive growth in the availability of potent genomically and immunologically targeted agents. Consequently, comprehensive analysis of every cancer is quickly becoming essential. The advent of clinical next generation sequencing technologies has fueled growth in precision oncology. Genomic testing permits the interrogation of the inside of the cell and the definition of a tumor’s precise coding sequence. Technology is evolving at a breathtaking pace. Sequencing a human genome was first performed for about $3 billion dollars in 2003, yet currently costs about $1000. Because of this rapid evolution, defining the best technology for patients is a moving target. Multiplex, pan-cancer, next-generation sequencing (NGS) has tremendous advantages over the current 1-drug, 1-gene test model: tissue is not wasted with multiple individual tests, a comprehensive genomic portfolio is created, and multiplex testing costs are lower than for numerous individual tests. However, the optimal panels are quickly evolving and include assessment of circulating tumor DNA from blood samples (liquid biopsies). Real-time ongoing reevaluation is needed. In this series, we invite authors to submit papers on:

  1. Next generation sequencing in cancers;
  2. Exceptional responders to precision cancer therapy;
  3. Next generation sequencing for immunotherapy and immuno-oncology;
  4. Broad NGS application in cancers
  5. Basket trials
  6. Genomic and Proteomic data from Public databases like TCGA.

Dr. Vivek Subbiah
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

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Research

Open AccessArticle Frequent Occurrence of NRAS and BRAF Mutations in Human Acral Naevi
Cancers 2019, 11(4), 546; https://doi.org/10.3390/cancers11040546
Received: 23 March 2019 / Revised: 9 April 2019 / Accepted: 10 April 2019 / Published: 16 April 2019
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Abstract
Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened [...] Read more.
Acral naevi are benign melanocytic tumors occurring at acral sites. Occasionally they can progress to become malignant tumors (melanomas). The genetics of acral naevi have not been assessed in larger studies. In our study, a large cohort of 130 acral naevi was screened for gene mutations known to be important in other naevi and melanoma subtypes by targeted next-generation sequencing. Mutation status was correlated with clinicopathological parameters. Frequent mutations in genes activating the MAP kinase pathway were identified, including n = 87 (67%) BRAF, n = 24 (18%) NRAS, and one (1%) MAP2K1 mutations. BRAF mutations were almost exclusively V600E (n = 86, 99%) and primarily found in junctional and compound naevi. NRAS mutations were either Q61K or Q61R and frequently identified in dermal naevi. Recurrent non-V600E BRAF, KIT, NF1, and TERT promoter mutations, present in acral melanoma, were not identified. Our study identifies BRAF and NRAS mutations as the primary pathogenic event in acral naevi, however, distributed differently to those in non-acral naevi. The mutational profile of acral naevi is distinct from acral melanoma, which may be of diagnostic value in distinguishing these entities. Full article
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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Open AccessFeature PaperArticle Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer
Cancers 2019, 11(4), 441; https://doi.org/10.3390/cancers11040441
Received: 8 February 2019 / Revised: 12 March 2019 / Accepted: 25 March 2019 / Published: 28 March 2019
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Abstract
Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result [...] Read more.
Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C>T) in all BCs and 16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk. Full article
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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Open AccessArticle A Simplified Genomic Profiling Approach Predicts Outcome in Metastatic Colorectal Cancer
Cancers 2019, 11(2), 147; https://doi.org/10.3390/cancers11020147
Received: 24 December 2018 / Revised: 19 January 2019 / Accepted: 22 January 2019 / Published: 27 January 2019
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Abstract
The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order [...] Read more.
The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on TP53 and/or RAS genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of TP53/RAS, the expected response is much worse compared to patients with exclusive TP53/RAS mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy. Full article
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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Open AccessFeature PaperArticle Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across Hematologic Malignancies: Implications for Next Generation Clinical Trials
Received: 19 November 2018 / Revised: 11 December 2018 / Accepted: 11 December 2018 / Published: 21 December 2018
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Abstract
Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) [...] Read more.
Background: The translation of genomic discoveries to the clinic is the cornerstone of precision medicine. However, incorporating next generation sequencing (NGS) of hematologic malignancies into clinical management remains limited. Methods: We describe 235 patients who underwent integrated NGS profiling (406 genes) and analyze the alterations and their potential actionability. Results: Overall, 227 patients (96.5%) had adequate tissue. Most common diagnoses included myelodysplastic syndrome (22.9%), chronic lymphocytic leukemia (17.2%), non-Hodgkin lymphoma (13.2%), acute myeloid leukemia (11%), myeloproliferative neoplasm (9.2%), acute lymphoblastic leukemia (8.8%), and multiple myeloma (7.5%). Most patients (N = 197/227 (87%)) harbored ≥1 genomic alteration(s); 170/227 (75%), ≥1 potentially actionable alteration(s) targetable by an FDA-approved (mostly off-label) or an investigational agent. Altogether, 546 distinct alterations were seen, most commonly involving TP53 (10.8%), TET2 (4.6%), and DNMT3A (4.2%). The median tumor mutational burden (TMB) was low (1.7 alterations/megabase); 12% of patients had intermediate or high TMB (higher TMB correlates with favorable response to anti-PD1/PDL1 inhibition in solid tumors). In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents. Full article
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
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