Alteration of the fragile histidine triad gene early in carcinogenesis: an update

2003 ◽  
Vol 3 (6) ◽  
pp. 291-296 ◽  
Author(s):  
Hideshi Ishii ◽  
Keiya Ozawa ◽  
Yusuke Furukawa
Keyword(s):  
Fragile Histidine Triad

scholarly journals Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Marcia Bellon ◽  
Izabela Bialuk ◽  
Veronica Galli ◽  
Xue-Tao Bai ◽  
Lourdes Farre ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Spastic Paraparesis ◽  
Cellular Transformation ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Fragile Histidine Triad ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Background Human 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. Methods Here, 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. Results We 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. Conclusions These 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.

The Mechanism of Action of the Fragile Histidine Triad, Fhit:  Isolation of a Covalent Adenylyl Enzyme and Chemical Rescue of H96G-Fhit†

Biochemistry ◽  
2004 ◽  
Vol 43 (23) ◽  
pp. 7637-7642 ◽  
Author(s):  
Kaisheng Huang ◽  
Abolfazl Arabshahi ◽  
Yaoming Wei ◽  
Perry A. Frey
Keyword(s):  
Mechanism Of Action ◽  
Chemical Rescue ◽  
Fragile Histidine Triad

Altered Expression of the Fragile Histidine Triad Gene in Primary Gastric Adenocarcinomas

2001 ◽  
Vol 284 (3) ◽  
pp. 850-855 ◽  
Author(s):  
Sang-Han Lee ◽  
Woo-Hyoung Kim ◽  
Hyun-Kyoung Kim ◽  
Kee-Min Woo ◽  
Hae-Seon Nam ◽  
...  
Keyword(s):  
Altered Expression ◽  
Fragile Histidine Triad ◽  
Gastric Adenocarcinomas

Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with myelodysplastic syndrome

2008 ◽  
Vol 32 (10) ◽  
pp. 1541-1545 ◽  
Author(s):  
Jiang Lin ◽  
Dong-ming Yao ◽  
Jun Qian ◽  
Ya-li Wang ◽  
Lan-xiu Han ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Methylation Status ◽  
Clinical Impact ◽  
Fhit Gene ◽  
Fragile Histidine Triad

Fragile Histidine Triad

2015 ◽  
pp. 1-5
Author(s):  
Catherine Waters ◽  
Helen Pace
Keyword(s):  
Fragile Histidine Triad
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