ArticleHuman genomics2018
Forward and reverse mutations in stages of cancer development.
Article in Human genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications.Scientific reports · 2025Article
- Forward-reverse mutation cycles in cancer cell lines under chemical treatments.Human genomics · 2024Article
- Detection of Structural Variations and Fusion Genes in Breast Cancer Samples Using Third-Generation Sequencing.Frontiers in cell and developmental biology · 2022Article
- Mutation or not, what directly establishes a neoplastic state, namely cellular immortality and autonomy, still remains unknown and should be prioritized in our research.Journal of Cancer · 2022Review
- Article
- Genomic subtyping of liver cancers with prognostic application.BMC cancer · 2020Article
- Biomarkers for Bladder Cancer Diagnosis and Surveillance: A Comprehensive Review.Diagnostics (Basel, Switzerland) · 2020Review
- The Need for Multi-Omics Biomarker Signatures in Precision Medicine.International journal of molecular sciences · 2019Review
- AluScanCNV2: An R package for copy number variation calling and cancer risk prediction with next-generation sequencing data.Genes & diseases · 2019Article
Corrections and comments
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Authors and funding
29 authors at 10 institutions in 2 countries.
Funding
Abstract
backgroundMassive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations.
methodsIn the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published "nontumor"-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined.
resultsWidespread GOHs enriched with CG-to-TG changes and associated with nearby CNVs and LOHs enriched with TG-to-CG changes were observed. Occurrences of GOH were 1.9-fold higher than LOH in "nontumor" tissues more than 2 cm away from the tumors, and a majority of these GOHs and LOHs were reversed in "paratumor" tissues within 2 cm of the tumors, forming forward-reverse mutation cycles where the revertant LOHs displayed strong lineage effects that pointed to a sequential instead of parallel development from "nontumor" to "paratumor" and onto tumor cells, which was also supported by the relative frequencies of 26 distinct classes of CNVs between these three types of cell populations.
conclusionsThese findings suggest that developing cancer cells undergo sequential changes that enable the "nontumor" cells to acquire a wide range of forward mutations including ones that are essential for oncogenicity, followed by revertant mutations in the "paratumor" cells to avoid growth retardation by excessive mutation load. Such utilization of forward-reverse mutation cycles as an adaptive mechanism was also observed in cultured HeLa cells upon successive replatings. An understanding of forward-reverse mutation cycles in cancer development could provide a genomic basis for improved early diagnosis, staging, and treatment of cancers.
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