Dataset Information

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients.

ABSTRACT:

Background and aims

Next generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear.

Results

TP53 (87%) and CDKN2A (20%) hot spot mutations were frequently found in early lesions. TP53 was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by CDKN2A (29%, 28%, 16% and 10%, respectively); the frequency of other mutations increased as the disease advanced (p < 0.01). Copy number variation analysis revealed copy number aberrations in multiple genes, including PIK3CA amplification (48%). NGS was superior to p53 immunostaining for detecting TP53 mutations (74% vs. 87%); in combination, the two tests improved detectability to 94%. Clinically, smoking was associated with the occurrence of TP53 mutations in these early lesions (p = 0.049).

Materials and methods

Fifty-four early esophageal neoplasia lesions from 47 patients treated by endoscopic resection (low-grade intraepithelial neoplasia [LGIN], n = 1; high-grade intraepithelial neoplasia [HGIN] n = 7; invasion limited to epithelium [EP/M1], n = 18; lamina propria mucosae [LPM/M2], n = 19; muscularis mucosae [MM/M3], n = 8; and upper third of the SM [SM1], n = 2) were isolated from formalin-fixed paraffin-embedded tissue specimens by laser-capture microdissection. Target sequencing of 50 cancer-related genes was performed with an Ion Proton sequencer; their association with the clinical characteristics was investigated.

Conclusions

Mutations of TP53 and CDKN2A, and PIK3CA amplification were common in early esophageal squamous neoplasia, while other mutations accumulated with disease progression. An understanding of these molecular events might provide a molecular basis for early lesion treatment.

SUBMITTER: Kobayashi S

PROVIDER: S-EPMC6298401 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients.

Kobayashi Shoji S Yamaguchi Tatsuya T Maekawa Shinya S Takano Shinichi S Kuno Toru T Tanaka Keisuke K Tsukui Yuya Y Iwamoto Fumihiko F Yoshida Takashi T Asakawa Yukiko Y Fukasawa Mitsuharu M Nakayama Yasuhiro Y Inoue Taisuke T Uetake Tomoyoshi T Sakamoto Minoru M Ohtaka Masahiko M Sato Tadashi T Enomoto Nobuyuki N

Oncotarget 20181204 95

<h4>Background and aims</h4>Next generation sequencing (NGS) has revealed a great deal about cancer-related somatic changes in esophageal squamous cell neoplasia; however, the changes in the very early stages remain unclear.<h4>Results</h4><i>TP53</i> (87%) and <i>CDKN2A</i> (20%) hot spot mutations were frequently found in early lesions. <i>TP53</i> was the most common mutation (LGIN/HGIN, 86%; EP, 83%; LPM, 95%; MM/SM1, 80%), followed by <i>CDKN2A</i> (29%, 28%, 16% and 10%, respectively); the ...[more]

PMID: 30613367

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Project description:Smoking and alcohol consumption are major risk factors for the development of esophageal squamous cell carcinoma (ESCC). Recent studies have demonstrated that smoking and alcohol consumption may be associated with altered DNA methylation in human cancer development. The aim of the present study was to evaluate methylation-modulated protein expression of tumor-related genes (TRGs) in the early stages of esophageal squamous neoplasia (ESN). ESN tissue samples (n=141) comprising 19 cases of low-grade intraepithelial neoplasia (LGIN), 70 of high-grade intraepithelial neoplasia/carcinoma in situ (HGIN/CIS) and 52 of invasive cancer, were endoscopically resected. The methylation-modulated protein expression of 5 TRGs [fragile histidine triad (FHIT), E-cadherin, MutL homolog 1 (MLH1) /MutS homolog 2 (MSH2) and cyclooxygenase-2 (COX-2)] as well as p53 was examined with immunohistochemistry, and their expression was compared with patient clinicopathological characteristics. Reduced or loss of FHIT, E-cadherin, MLH1/MSH2 and COX-2 expression was detected in 26.3 (5/19), 5.3 (1/19), 0 (0/19) and 63.2% (12/19) of LGIN cases, 61.4 (43/70), 18.6 (13/70), 7.1 (5/70) and 65.7% (46/70) of HGIN/CIS cases, and 78.8 (41/52), 50.0 (26/52), 11.5 (6/52) and 59.6% (31/52) of invasive cancer cases, respectively. Reduced or absent expression of FHIT and E-cadherin was significantly associated with neoplastic progression (FHIT, P=0.0007; E-cadherin, P=0.00014). The mean number of TRGs (FHIT, E-cadherin, MLH1/MSH2, and COX-2) that exhibited reduced or absent expression in LGIN, HGIN/CIS and invasive cancer specimens was 1.12±0.61, 1.66±0.93 and 2.09±0.96, respectively, demonstrating a significant stepwise increment from LGIN to HGIN/CIS and then to invasive cancer (P<0.05). p53 overexpression was frequently detected in ESN with head and neck carcinomas. However p53 overexpression was not significantly associated with ESN progression. An increase in the number of the 5 TRG proteins with reduced or loss of expression in the early stages of esophageal tumorigenesis was demonstrated, and their decreased expression was observed to be associated with tumor progression. Therefore, smoking and alcohol drinking may be associated with not only carcinogenesis but also the progression of ESN.

Dataset Information

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients.

Background and aims

Results

Materials and methods

Conclusions

Publications

Target sequencing of cancer-related genes in early esophageal squamous neoplasia resected by endoscopic resection in Japanese patients.

Similar Datasets

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