Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System

Yachida, Shinichi; Totoki, Yasushi; Noë, Michaël; Nakatani, Yoichiro; Horie, Masafumi; Kawasaki, Kenta; Nakamura, Hiromi; Saito‐Adachi, Mihoko; Suzuki, Masami; Takai, Erina; Hama, Natsuko; Higuchi, Ryota; Hirono, Seiko; Shiba, Satoshi; Kato, Mamoru; Furukawa, Eisaku; Arai, Yasuhito; Rokutan, Hirofumi; Hashimoto, Taiki; Mitsunaga, Shuichi; Kanda, Mitsuro; Tanaka, Hidenori; Takata, So; Shimomura, Ayaka; Oshima, Masaharu; Hackeng, Wenzel M.; Okumura, Tomoyuki; Okano, Keiichi; Yamamoto, Masakazu; Yamaue, Hiroki; Morizane, Chigusa; Arihiro, Koji; Furukawa, Toru; Sato, Toshiro; Kiyono, Tohru; Brosens, Lodewijk A.A.; Wood, Laura D.; Hruban, Ralph H.; Shibata, Tatsuhiro

doi:10.1158/2159-8290.cd-21-0669

Cited by 69 publications

(95 citation statements)

References 75 publications

(115 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The collection of 60 GI-NECs analyzed included pancreatic, colorectal, gastric, biliary, ampullary and esophageal tumors, while the remaining 55 GI-NET samples included pancreatic, colorectal and duodenal. Analysis of mutations allowed GI-NECs to be distinguished from GI-NETs, with GI-NECs containing mutations in TP53 , KRAS , RB1 , CCNE1 , CDKN2A and MYC ( 43 ).…”

Section: Genetic Basis Of Gep-nensmentioning

confidence: 99%

“…also evaluated methylation profiles and using unsupervised hierarchical cluster analysis of methylation status, divided their samples into three groups. pNETs were grouped into one group, non-pNETs in another, and the remaining group featured a CpG island methylator phenotype (CIMP) due to alterations in genes related to DNA methylation and/or due to MLH1 promoter hypermethylation ( 43 ).…”

Section: Dna Methylationmentioning

confidence: 99%

See 1 more Smart Citation

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

Crabtree

2022

Front. Oncol.

View full text Add to dashboard Cite

Gastroenteropancreatic neuroendocrine neoplasms are a rare, diverse group of neuroendocrine tumors that form in the pancreatic and gastrointestinal tract, and often present with side effects due to hormone hypersecretion. The pathogenesis of these tumors is known to be linked to several genetic disorders, but sporadic tumors occur due to dysregulation of additional genes that regulate proliferation and metastasis, but also the epigenome. Epigenetic regulation in these tumors includes DNA methylation, chromatin remodeling and regulation by noncoding RNAs. Several large studies demonstrate the identification of epigenetic signatures that may serve as biomarkers, and others identify innovative, epigenetics-based targets that utilize both pharmacological and theranostic approaches towards the development of new treatment approaches.

show abstract

Section: Genetic Basis Of Gep-nensmentioning

confidence: 99%

Section: Dna Methylationmentioning

confidence: 99%

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

Crabtree

2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The study implies that metagenome-based physiological dysfunction in the intestinal microenvironment drives the disease-progression state of individuals with rectal NETs. For viruses, two kinds of GEP-NECs are etiologically related to viruses: MCPyV acts on gastric NECs, and HPV acts on colorectal NECs [ 100 ]. However, reports of fungal involvement in tumors remain to be explored.…”

Section: Microbial Communitymentioning

confidence: 99%

The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms

Chen

et al. 2022

Cancers

View full text Add to dashboard Cite

Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.

show abstract

“…Alterations in the Notch gene family are characteristic of nonpancreatic NECs. The transcription factors, mainly the SOX2 gene, are overexpressed in most GI-NECs[ 30 ].…”

Section: Molecular Factors – Genomic Profilementioning

confidence: 99%

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

Pavlidis¹,

Pavlidis²

2022

WJCC

View full text Add to dashboard Cite

The prevalence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing, and despite recent advances in their therapy, it remains inadequate in patients with advanced well-differentiated neuroendocrine tumors. These tumors present many challenges concerning the molecular basis and genomic profile, pathophysiology, clinicopathological features, histopathologic classification, diagnosis and treatment. There has been an ongoing debate on diagnostic criteria and clinical behavior, and various changes have been made over the last few years. Neuroendocrine carcinoma of the gastrointestinal system is a rare but highly malignant neoplasm that is genetically distinct from gastrointestinal system neuroendocrine tumors (NETs). The diagnosis and management have changed over the past decade. Emerging novel biomarkers and metabolic players in cancer cells are useful and promising new diagnostic tools. Progress in positron emission tomography-computerized tomography and scintigraphy with new radioactive agents ( 64 Cu-DOTATATE or 68 Ga-DOTATATE) replacing enough octreoscan, has improved further the current diagnostic imaging. Promising results provide targeted therapies with biological agents, new drugs, chemotherapy and immunotherapy. However, the role of surgery is important, since it is the cornerstone of management. Simultaneous resection of small bowel NETs with synchronous liver metastases is a surgical challenge. Endoscopy offers novel options not only for diagnosis but also for interventional management. The therapeutic option should be individualized based on current multidisciplinary information.

show abstract

Comprehensive Genomic Profiling of Neuroendocrine Carcinomas of the Gastrointestinal System

Cited by 69 publications

References 75 publications

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms

Molecular factors, diagnosis and management of gastrointestinal tract neuroendocrine tumors: An update

Contact Info

Product

Resources

About