ArticleMolecular cancer2021
Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 15 citations in OpenAlex.
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- Loss of Heterozygosity in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma - A Scoping Review.Head and neck pathology · 2025Article
- Closing the gaps, and improving somatic structural variant analysis and benchmarking using CHM13-T2T.Genome research · 2025Article
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- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- Effects of DNA methylation and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2024Review
- IncreasedInternational journal of molecular sciences · 2024Article
- The benefit of a complete reference genome for cancer structural variant analysis.medRxiv : the preprint server for health sciences · 2024Article
- Epigenetic Abnormalities in Chondrosarcoma.International journal of molecular sciences · 2023Review
- Deep learning for detecting and elucidating human T-cell leukemia virus type 1 integration in the human genome.Patterns (New York, N.Y.) · 2023Article
- Feedback Loop Regulation between Pim Kinases and Tax Keeps Human T-Cell Leukemia Virus Type 1 Viral Replication in Check.Journal of virology · 2022Article
- FHIT as a biomarker for early screening of adult T-cell leukemia.Journal of cancer biology · 2021Article
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Authors and funding
17 authors at 10 institutions in 6 countries.
Funding
Abstract
backgroundHuman T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation.
methodsHere, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples.
resultsWe found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation.
conclusionsThese results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits.
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