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Cancers
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Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy
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Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 25 October 2024 | Viewed by 7932

Special Issue Editor

Dr. Haruhiko Takeda

E-Mail Website
Guest Editor
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
Interests: liver cancer; hepatocarcinogenesis; genetic analysis; next-generation sequencing; clonal evolution; molecular targeted therapy; therapeutic biomarker; precision medicine

Special Issue Information

Dear Colleagues,

Recent progress in next-generation sequencing has enabled the comprehensive genetic profiling of various cancers, including gastrointestinal, hepatobiliary and pancreatic cancer. After the international projects for cancer genome analyses, the landscape of the driver genes and genetic heterogeneity have been identified in each type of cancer. Importantly, the genetic profile of every tumor differs from one another, and the accumulating knowledge has revealed that the anti-tumor effect by molecular targeted therapies can be influenced by the interpatient heterogeneity of genetic aberrations. Although genetic analyses on clinical cohorts have been conducted worldwide, the pivotal molecular targets and biomarkers predicting the treatment efficacy have not sufficiently been established to date in many sorts of cancer.

The aim of this Special Issue is to present the recent progress on the clinical application of genetic analysis, including the identification of novel therapeutic targets, the early cancer detection, and the exploration of predictive biomarkers based on any genetic testing, which should lead to the realization of the precision medicine. We are inviting relevant original research, systematic reviews, meta-analyses, and short communications covering the above-mentioned topics.

Dr. Haruhiko Takeda
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 submissions that pass pre-check are 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 semimonthly 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 2900 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.

Keywords

  • cancer genome analysis
  • next-generation sequencing
  • heterogeneity
  • molecular targeted therapy
  • therapeutic biomarker
  • precision medicine

Published Papers (3 papers)

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Research

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14 pages, 1931 KiB  
Article
HotSPOT: A Computational Tool to Design Targeted Sequencing Panels to Assess Early Photocarcinogenesis
by Sydney R. Grant, Spencer R. Rosario, Andrew D. Patentreger, Nico Shary, Megan E. Fitzgerald, Prashant K. Singh, Barbara A. Foster, Wendy J. Huss, Lei Wei and Gyorgy Paragh
Cancers 2023, 15(5), 1612; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051612 - 05 Mar 2023
Cited by 1 | Viewed by 1823
Abstract
Mutations found in skin are acquired in specific patterns, clustering around mutation-prone genomic locations. The most mutation-prone genomic areas, mutation hotspots, first induce the growth of small cell clones in healthy skin. Mutations accumulate over time, and clones with driver mutations may give [...] Read more.
Mutations found in skin are acquired in specific patterns, clustering around mutation-prone genomic locations. The most mutation-prone genomic areas, mutation hotspots, first induce the growth of small cell clones in healthy skin. Mutations accumulate over time, and clones with driver mutations may give rise to skin cancer. Early mutation accumulation is a crucial first step in photocarcinogenesis. Therefore, a sufficient understanding of the process may help predict disease onset and identify avenues for skin cancer prevention. Early epidermal mutation profiles are typically established using high-depth targeted next-generation sequencing. However, there is currently a lack of tools for designing custom panels to capture mutation-enriched genomic regions efficiently. To address this issue, we created a computational algorithm that implements a pseudo-exhaustive approach to identify the best genomic areas to target. We benchmarked the current algorithm in three independent mutation datasets of human epidermal samples. Compared to the sequencing panel designs originally used in these publications, the mutation capture efficacy (number of mutations/base pairs sequenced) of our designed panel improved 9.6–12.1-fold. Mutation burden in the chronically sun-exposed and intermittently sun-exposed normal epidermis was measured within genomic regions identified by hotSPOT based on cutaneous squamous cell carcinoma (cSCC) mutation patterns. We found a significant increase in mutation capture efficacy and mutation burden in cSCC hotspots in chronically sun-exposed vs. intermittently sun-exposed epidermis (p < 0.0001). Our results show that our hotSPOT web application provides a publicly available resource for researchers to design custom panels, enabling efficient detection of somatic mutations in clinically normal tissues and other similar targeted sequencing studies. Moreover, hotSPOT also enables the comparison of mutation burden between normal tissues and cancer. Full article
(This article belongs to the Special Issue Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy)
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20 pages, 7167 KiB  
Article
Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy
by Rodrigo González-Barrios, Nicolás Alcaraz, Michel Montalvo-Casimiro, Alejandra Cervera, Cristian Arriaga-Canon, Paulina Munguia-Garza, Diego Hinojosa-Ugarte, Nora Sobrevilla-Moreno, Karla Torres-Arciga, Julia Mendoza-Perez, José Diaz-Chavez, Carlo Cesar Cortes-González, Clementina Castro-Hernández, Jorge Martínez-Cedillo, Ana Scavuzzo, Delia Pérez-Montiel, Miguel A. Jiménez-Ríos and Luis A. Herrera
Cancers 2022, 14(9), 2065; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092065 - 20 Apr 2022
Cited by 5 | Viewed by 2756
Abstract
Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this [...] Read more.
Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population. Full article
(This article belongs to the Special Issue Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy)
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Review

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13 pages, 926 KiB  
Review
Genomic and Epigenomic Characterization of Tumor Organoid Models
by Chehyun Nam, Benjamin Ziman, Megha Sheth, Hua Zhao and De-Chen Lin
Cancers 2022, 14(17), 4090; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174090 - 24 Aug 2022
Cited by 3 | Viewed by 2669
Abstract
Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and [...] Read more.
Tumor organoid modeling has been recognized as a state-of-the-art system for in vitro research on cancer biology and precision oncology. Organoid culture technologies offer distinctive advantages, including faithful maintenance of physiological and pathological characteristics of human disease, self-organization into three-dimensional multicellular structures, and preservation of genomic and epigenomic landscapes of the originating tumor. These features effectively position organoid modeling between traditional cell line cultures in two dimensions and in vivo animal models as a valid, versatile, and robust system for cancer research. Here, we review recent advances in genomic and epigenomic characterization of tumor organoids and the novel findings obtained, highlight significant progressions achieved in organoid modeling of gene–drug interactions and genotype–phenotype associations, and offer perspectives on future opportunities for organoid modeling in basic and clinical cancer research. Full article
(This article belongs to the Special Issue Genome Sequencing of Cancer: Identifying Targets and Biomarkers for Therapy)
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