High prevalence of <i>TERT</i> aberrations in myxoid liposarcoma: <i>TERT</i> reactivation may play a crucial role in tumorigenesis

Kunieda, Junko; Yamashita, Kyoko; Togashi, Yosuke; Baba, Satoko; Sakata, Seiji; Inamura, Kentaro; Ae, Keisuke; Matsumoto, Seiichi; Machinami, Rikuo; Kitagawa, Masanobu; Takeuchi, Kengo

doi:10.1111/cas.15256

Cited by 12 publications

(15 citation statements)

References 58 publications

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“…11,12 Despite recent advances in surgery, radiotherapy, and novel treatment strategies, the overall 5-year survival rate of patients with RPLs remains at approximately 50%. 13,14 In previous studies, a large number of clinical and histopathological features and therapeutic strategies have been investigated to predict and improve the prognosis of RPLs. [15][16][17][18][19][20] With the increased understanding of human health and the consequent advancements in healthcare, the role of socio-psychosocial factors in cancer is receiving increased attention.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, recent studies have demonstrated that novel therapeutic strategies, including targeted drugs, are effective for treating RPLs 11,12 . Despite recent advances in surgery, radiotherapy, and novel treatment strategies, the overall 5‐year survival rate of patients with RPLs remains at approximately 50% 13,14 …”

Section: Introductionmentioning

confidence: 99%

“… 11 , 12 Despite recent advances in surgery, radiotherapy, and novel treatment strategies, the overall 5‐year survival rate of patients with RPLs remains at approximately 50%. 13 , 14 …”

Section: Introductionmentioning

confidence: 99%

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Effects of marital status on survival of retroperitoneal liposarcomas stratified by age and sex: A population‐based study

Zhang

et al. 2022

Cancer Medicine

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Background Previous studies have shown that marital status is associated with survival in patients with a variety of cancer types, including lung cancer, prostate cancer, and bladder cancer. However, to date, the impact of marital status on the survival of patients with retroperitoneal liposarcomas (RPLs) has not been established. Methods A total of 1211 eligible patients diagnosed with RPLs were identified in the Surveillance, Epidemiology, and End Results (SEER) database. The relationships between marital status and survival in patients with RPLs were assessed. Patients were stratified by age to determine whether an association exists between marital status and age. We also probed the association between marital status and survival in males and females. Results Our findings suggest that divorced, separated, or widowed patients have more advanced cancer stages, and more of these patients do not undergo surgery. Meanwhile, divorced, separated, or widowed patients have worse survival outcomes than married patients (overall survival (OS): HR = 1.66 (95% CI, 1.12, 2.46)); cancer‐specific survival (CSS): HR = 1.90 (95% CI, 1.13, 3.19)). OS does not differ between single patients and married patients (HR = 1.21 [95% CI, 0.81, 1.81]) or CSS (HR = 1.36 [95% CI, 0.80, 2.29]). In addition, these results demonstrate that being divorced, separated, or widowed can play a significant detrimental role in mortality in older and female patients. Conclusion Married patients have earlier disease stages at diagnosis and better survival outcomes than divorced, separated, or widowed patients with RPLs. In addition, this effect is especially pronounced in older people and females.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of marital status on survival of retroperitoneal liposarcomas stratified by age and sex: A population‐based study

Zhang

et al. 2022

Cancer Medicine

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“…Telomerase reverse transcriptase (TERT) promoter mutation has been found in human hepatobiliary, pancreatic, and gastrointestinal cancer cell lines (Hirata et al, 2022). The high frequency of hotspot mutations (C228T or C250T) in the promoter region of telomerase reverse transcriptase TERT that encodes the TERT protein has also been found in myxoid liposarcoma (Kunieda et al, 2021). PinX1, known as a potent TERT inhibitor, also contributes to cellular aging and cancer tumorigenicity.…”

Section: Discussionmentioning

confidence: 99%

Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1

et al. 2022

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New drugs or active leads with high efficiency and low toxicity are needed in the treatment of lung cancer. Natural products are an important source of anti-tumor drugs. At present, there are many molecular-targeted anti-tumor drugs derived from natural products or their derivatives for tumor treatment or in clinical trials. Hesperidin is a flavanone isolated from the Rutaceae plant lime Citrus aurantium L. or Citrus sinensis Osbeck. It has been considered to inhibit cancer cell viability in vitro. However, the effect of hesperidin on lung cancer and its underlying mechanism remain unclear. In this study, we found that the pinX1 expression level is closely related to overall survival and plays an important role in regulating lung cancer cell proliferation, migration, invasion, and senescence. More importantly, hesperidin significantly increased pinX1 protein expression, and knockdown pinX1 by its specific siRNA blocked the protective effects of hesperidin. Moreover, we also assessed that hesperidin at 100 mg/kg is safe in vivo. These findings showed that hesperidin is a potential therapeutic candidate for preventing the progression of lung cancer.

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“…Subsequently, two popular mutation sites, C228T and C250T, were also found in adrenal tumors, which can promote the expression of hTERT and increase the activity of telomerase, providing a suitable environment for tumor growth [25]. In addition, scientists have successively found mutations in the hTERT promoter region in thyroid cancer [26], liposarcoma [27], hepatocellular carcinoma [28], urothelial cancer and other tumors [29,30], but the mutation sites and mutation frequencies were not the same. Since the first discovery of TERT promoter mutations in melanoma, an increasing number of studies have shown that TERT promoter mutations play an important role in tumorigenesis [31,32].…”

Section: Introductionmentioning

confidence: 99%

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

Xiang

Chen

et al. 2022

Vet Res

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Avian leukosis virus subgroup J (ALV-J) can cause neoplastic diseases in poultry and is still widely prevalent in China. Chicken telomerase reverse transcriptase (chTERT) is the core component of telomerase, which is closely related to the occurrence and development of tumors. Our previous studies showed that chTERT is overexpressed in ALV-J tumors, but the mechanism is still not completely clear. Therefore, this study aims to analyze the possible molecular mechanism of chTERT overexpression in ALV-J tumors from the perspective of DNA methylation and promoter mutation. Methylation sequencing of the chTERT amplicon showed that ALV-J replication promoted the methylation level of the chTERT promoter. And the methylation level of the chTERT promoter in ALV-J tumors was significantly higher than that in tumor-adjacent and normal tissues. Compared with the tumor-adjacent and normal tissues, the chTERT promoter in each ALV-J tumors tested had a mutation of −183 bp C > T, and 36.0% (9/25) of the tumors also had mutations of −184 bp T > C, −73 bp::GGCCC and −56 bp A > T in the chTERT promoter, which formed the binding sites for the transcription factors NFAT5, TFAP2A and ZEB1, respectively. The results of RT–qPCR and Western blotting showed that the occurrence of these mutations significantly increased the expression level of chTERT. In conclusion, this study demonstrated that the high expression of chTERT in ALV-J tumors is positively correlated with the level of hypermethylation and mutation in its promoter, which provides a new perspective for further research on the molecular mechanism of chTERT in ALV-J tumorigenesis.

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High prevalence of TERT aberrations in myxoid liposarcoma: TERT reactivation may play a crucial role in tumorigenesis

Cited by 12 publications

References 58 publications

Effects of marital status on survival of retroperitoneal liposarcomas stratified by age and sex: A population‐based study

Effects of marital status on survival of retroperitoneal liposarcomas stratified by age and sex: A population‐based study

Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1

The expression level of chicken telomerase reverse transcriptase in tumors induced by ALV-J is positively correlated with methylation and mutation of its promoter region

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