Genetic landscape of esophageal squamous cell carcinoma

Gao, Yubin; Chen, Zhao Li; Li, Jia Gen; Hu, Xue; Shi, Xue Jiao; Sun, Zeng Miao; Zhang, Fan; Zhao, Zi Ran; Li, Zi Tong; Liu, Zi Yuan; Zhao, Yu; Sun, Jian; Zhou, Cheng; Yao, Ran; Wang, Su Ya; Wang, Pan; Sun, Nan; Zhang, Bai Hua; Dong, Jing; Yu, Yue; Luo, Mei; Feng, Xiao Li; Shi, Su Sheng; Zhou, Fang; Tan, Feng; Qiu, Bin; Li, Ning; Shao, Kwang‐Tsao; Zhang, Li Jian; Zhang, Lan Jun; Xue, Qi; Gao, Shu Geng; He, Jie

doi:10.1038/ng.3076

Cited by 576 publications

(680 citation statements)

References 86 publications

Supporting

Mentioning

614

Contrasting

Unclassified

Order By: Relevance

“…As we have described, the tumor suppressor role of Notch was relatively well established in CSCC, unlike for HNSCC 43. Until recently, the NOTCH1 has drawn much attention as it was identified as one of the most frequently mutated genes in SCCs of cutaneous 5, head and neck 6, 7, 53, esophageal 8, 56, and lungs 88. We summarized the NOTCH1 mutation patterns in five different SCCs, and explored the biological consequences of these mutations based on the Up‐to‐date structural information of Notch signaling.…”

Section: Resultsmentioning

confidence: 94%

“…Notably, different NOTCH1 alternation patterns were observed in patients from different ethnical populations: NOTCH1 appears to mutate more frequently in North American ESCCs (21%) than Chinese ESCCs (2%). However, this concept was questioned by a later genetic landscape of ESCC samples of Chinese ancestry, which identified a high NOTCH ( NOTCH1‐3 ) alteration frequency (13%) in Chinese cases 56.…”

Section: Notch Signaling In Head and Neck Squamous Cell Carcinoma (Hnmentioning

confidence: 99%

See 1 more Smart Citation

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

View full text Add to dashboard Cite

The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

show abstract

Section: Resultsmentioning

confidence: 94%

Section: Notch Signaling In Head and Neck Squamous Cell Carcinoma (Hnmentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Correlation between RKIP protein expression and clinicopathological characteristics. epigenetic alterations also play significant roles in the development of multiple cancers, including ESCC (30)(31)(32). Among various epigenetic alterations, aberrant DNA methylation (including hypomethylation of oncogenes and hypermethylation of tumor suppressor genes) is the best characterized and most crucial mechanism modulating chromatin structure and the expression levels of oncogenes or tumor suppressor genes, contributing to tumor initiation and further development (33).…”

Section: Discussionmentioning

confidence: 99%

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

et al. 2017

View full text Add to dashboard Cite

Abstract. Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and its downregulation is associated with distinct human cancers. In the present study, the status of RKIP promoter methylation, as well as its expression and clinical significance in esophageal squamous cell carcinoma (ESCC), were examined. The promoter methylation status in the 5'-CpG island of the RKIP gene and the expression level of the RKIP protein were examined using a modified methylation-specific polymerase chain reaction (MSP) method and immunohistochemical staining, respectively, in 77 ESCC samples and matched paratumor normal tissues. The incidence of RKIP promoter methylation was significantly higher in tumor samples (75.3%) than in the matched normal tissues (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in poorly differentiated cancers (93.5%) compared with well-differentiated cancers (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001). Consistent with the promoter methylation status, the expression level of RKIP was significantly reduced in cancer tissues (36.4%) compared with matched normal tissues (76.6%; P<0.01), as well as in cancers with positive lymph node metastasis (24.4%) compared with those with negative lymph node metastasis (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly correlated with the down regulation of RKIP and the development of ESCC. The results of the present study suggested that the methylation status of the RKIP promoter, when combined with its expression level, may serve as a biomarker for predicting the biological behaviors of ESCC.

show abstract

“…Because of the risk factors commonly associated with the development of ESCC and HNSCC, several studies have revealed that ESCC and HNSCC have similar molecular alterations (1)(2)(3)(4)(5)(6)(7)(8). For instance, cyclin D1, p53, EGFR, and c-myc are common important genetic alterations in ESCC and HNSCC carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC

Nakamura

Togashi

Nakahara

et al. 2016

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib.

show abstract

Genetic landscape of esophageal squamous cell carcinoma

Cited by 576 publications

References 86 publications

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Promoter methylation and expression of Raf kinase inhibitory protein in esophageal squamous cell carcinoma

Afatinib against Esophageal or Head-and-Neck Squamous Cell Carcinoma: Significance of Activating Oncogenic HER4 Mutations in HNSCC

Contact Info

Product

Resources

About