The ACIN1 Gene is Hypermethylated in Early Stage Lung Adenocarcinoma

Shu, Yujian; Iijima, Tatsuo; Sun, Weihong; Kano, Junko; Ishiyama, Takamitsu; Okubo, Chigusa; Anami, Yoichi; Tanaka, Ryota; Fukai, Shimao; Noguchi, Masayuki

doi:10.1097/01243894-200602000-00010

Cited by 9 publications

(15 citation statements)

References 18 publications

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“…DNA methylation markers may be useful because of their chemical stability and because they are relatively easy to detect. Shu et al observed hypermethylation of the ACIN1 gene in some non-tumorous regions of ADC as well as in early stage lung ADC [14]. They suggested that methylation of ACIN1 is one of the earliest events in lung ADC development and suggested that it may be possible to identify individuals with a high risk of developing lung ADC [14].…”

Section: Discussionmentioning

confidence: 92%

“…Several investigators have attempted to develop molecular markers to detect pulmonary ADC [14,38]. DNA methylation markers may be useful because of their chemical stability and because they are relatively easy to detect.…”

Section: Discussionmentioning

confidence: 99%

“…Somatic mutations and increased expression of p53 were detected in advanced ADC [13]. While genetic alterations have been extensively studied in the multistep carcinogenesis model in the peripheral airway, epigenetic abnormalities have not been identified [2,3,6,7,9,10,14,15].…”

Section: Introductionmentioning

confidence: 97%

“…Shu et al suggested that the aberrant CpG island methylation of ACIN1 is one of the earliest events in lung ADC development [14]. Kubo et al identified that hypermethylation of p16 INK4a , CDH13, and RASSF1A was related to the acquirement of invasiveness in small peripheral ADC [15].…”

Section: Introductionmentioning

confidence: 99%

“…There are few hypermethylated genes in the development of small ADC sequence [14,15]. Shu et al suggested that the aberrant CpG island methylation of ACIN1 is one of the earliest events in lung ADC development [14].…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation profile during multistage progression of pulmonary adenocarcinomas

et al. 2011

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Multiple genetic and epigenetic alterations are known to be involved in the carcinogenesis of peripheral pulmonary adenocarcinoma (ADC). However, epigenetic abnormalities have not been extensively investigated in the following multistage progression sequence: atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to invasive ADC. To determine the potential role of promoter methylation during ADC development of the lung, we examined methylation status in 20 normal, 20 AAH, 30 AIS, and 60 ADC lung tissues and compared methylation status among the lesions. The MethyLight assay was used to determine the methylation status of 18 CpG island loci, which were hypermethylated in ADC compared to noncancerous lung tissues. The mean number of methylated CpG island loci was significantly higher in ADC than in AAH and AIS, (p < 0.003 between ADC and AAH, p < 0.005 between ADC and AIS). Aberrant methylation of HOXA1, TMEFF2, and RARB was frequently observed in preinvasive lesions, including AAH and AIS. Furthermore, methylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was significantly more frequent in invasive ADC than AAH or AIS. Our results indicate that epigenetic alterations are involved in the multistep progression of pulmonary ADC development, and aberrant CpG island methylation accumulates during multistep carcinogenesis. In addition, aberrant methylation of HOXA1, TMEFF2, and RARB occurred in preinvasive lesions, which indicates that epigenetic alterations of these genes are involved in the early stages of pulmonary ADC development. In contrast, hypermethylation of PENK, BCL2, RUNX3, DLEC1, MT1G, GRIN2B, CDH13, CCND2, and HOXA10 was more frequent in invasive ADC than in preinvasive lesions, which indicates that methylation of these genes occurs later during tumor invasion in the AAH-AIS-ADC sequence.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA methylation profile during multistage progression of pulmonary adenocarcinomas

et al. 2011

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Whole-Organ Genomic Characterization of Mucosal Field Effects Initiating Bladder Carcinogenesis

et al. 2019

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Graphical AbstractHighlights d Field change in DNA methylation is the initiator of bladder carcinogenesis d The methylation changes suppressed immunity and dysregulated Ras-related pathways d Founder ACIN1 mutation in normal mucosa clonally expanded in progression to carcinoma d Cells with mutations of 22 genes expanded clonally with progression to carcinoma SUMMARYWe used whole-organ mapping to study the locoregional molecular changes in a human bladder containing multifocal cancer. Widespread DNA methylation changes were identified in the entire mucosa, representing the initial field effect. The field effect was associated with subclonal low-allele frequency mutations and a small number of DNA copy alterations. A founder mutation in the RNA splicing gene, ACIN1, was identified in normal mucosa and expanded clonally with an additional 21 mutations in progression to carcinoma. The patterns of mutations and copy number changes in carcinoma in situ and foci of carcinoma were almost identical, confirming their clonal origins. The pathways affected by the DNA copy alterations and mutations, including the Kras pathway, were preceded by the field changes in DNA methylation, suggesting that they reinforced mechanisms that had already been initiated by methylation. The results demonstrate that DNA methylation can serve as the initiator of bladder carcinogenesis.

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The roles of m6A methylation in cervical cancer: functions, molecular mechanisms, and clinical applications

Mao,

Wang,

Zhang

et al. 2023

Cell Death Dis

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Cervical cancer (CC) is a gynecological neoplasm with the highest incidence rate, primarily attributed to the persistent infection of high-risk Human papillomavirus (HPV). Despite extensive research, the pathogenesis of CC remains unclear. N6-methyladenosine (m6A) methylation, the most prevalent form of epigenetic modification in RNA, is intricately linked to cell proliferation, metastasis, metabolism, and therapeutic resistance within the tumor microenvironment (TME) of CC. The involvement of the writer, reader, and eraser in m6A modification impacts the advancement of tumors through the regulation of RNA stability, nuclear export, translation efficiency, and RNA degradation. Here, we discuss the biogenesis of m6A, the atypical expressions of m6A regulators, the mechanisms of molecular interactions, and their functions in CC. Furthermore, we elucidate m6A modification of non-coding RNA. In the context of precision medicine, and with the advancements of genomics, proteomics, and high-throughput sequencing technologies, we summarize the application of m6A in the clinical diagnosis and treatment of CC. Additionally, new perspectives on detection methods, immune regulation, and nano-drug development are presented, which lay the foundation for further research of m6A and provide new ideas for the clinical treatment of CC.

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The ACIN1 Gene is Hypermethylated in Early Stage Lung Adenocarcinoma

Cited by 9 publications

References 18 publications

DNA methylation profile during multistage progression of pulmonary adenocarcinomas

DNA methylation profile during multistage progression of pulmonary adenocarcinomas

Whole-Organ Genomic Characterization of Mucosal Field Effects Initiating Bladder Carcinogenesis

The roles of m6A methylation in cervical cancer: functions, molecular mechanisms, and clinical applications

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