Targeted next-generation sequencing of well-differentiated rectal, gastric, and appendiceal neuroendocrine tumors to identify potential targets

Park, Ha Young; Kwon, Mi Jung; Kang, Ho Suk; Kim, Yun Joong; Kim, Nan Young; Kim, Min Jeong; Min, Kyueng‐Whan; Choi, Kyung Chan; Nam, Eun Sook; Cho, Seong Jin; Park, Hye-Rim; Min, Soo Kee; Seo, Jinwon; Choe, Ji Young; Lee, Hye Kyung

doi:10.1016/j.humpath.2019.02.007

Cited by 30 publications

(26 citation statements)

References 32 publications

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“…Although neuroendocrine tumors are rare neoplasms, they have a malignant potential, and most of them occur in the gastrointestinal tract [23,24]. Even today, these tumors remain a clinical challenge because of their heterogeneity in biological behavior, diagnosis as well as treatment options.…”

Section: Discussionmentioning

confidence: 99%

Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

Huang

Qiu

et al. 2020

IEEE Access

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At present, early diagnosis and treatment is the most effective way to treat early gastrointestinal neuroendocrine tumors. Therefore, we attempted to carry out multiphoton imaging of early neuroendocrine tumors because of its ability to label-free image tissue microstructure at the cellular level. Imaging results show that this imaging technique can quickly identify the histopathological changes in mucosa and submucosa caused by tumor invasion. Furthermore, we performed automatic image analysis on SHG images and extracted two optical diagnostic features-collagen density and average intensity, and also found obvious differences in the density as well as average intensity of collagen fibers in tumor microenvironment using a series of quantitative analysis. These findings may further facilitate the development of multiphoton microscopic imaging technique for clinical use. INDEX TERMS Multiphoton imaging, image analysis, gastrointestinal neuroendocrine tumors.

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Section: Discussionmentioning

confidence: 99%

Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

Huang

Qiu

et al. 2020

IEEE Access

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“…This represents a novel finding that expands the clinical spectrum of LFS. Although TP53 somatic mutations are frequently found in neuroendocrine carcinoma, they do not commonly appear in well-differentiated NET with prolonged disease-free survival, such as in this patient [2,5,6].…”

Section: Discussionmentioning

confidence: 65%

“…Prior studies demonstrate somatic TP53 mutations in all grades of NET from various primary sites, with high-grade tumors more commonly harboring the mutation in both intra-abdominal and extra-abdominal NETs. Overall, more than half of poorly differentiated GI NECs have somatic TP53 mutations, while 0-11% of moderately and well-differentiated GI NETs harbor the mutation [2,5,10,11]. Similarly, for pulmonary NETs, more than 60% of small cell lung cancer and large cell neuroendocrine carcinoma have TP53 mutations, and 0-11% of well-differentiated grade 1 and 2 pulmonary NETs have been shown to have TP53 mutations [12,13].…”

Section: Discussionmentioning

confidence: 99%

“…Although somatic TP53 mutations have been identified in various grades of PNETs as well as gastric, small bowel, colorectal, and appendiceal neuroendocrine tumors (NETs), there are no reported cases of NETs associated with a germline TP53 mutation [2,5,6]. TP53 mutations are commonly found in poorly differentiated neuroendocrine carcinomas [2].…”

Section: Introductionmentioning

confidence: 99%

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The first pancreatic neuroendocrine tumor in Li-Fraumeni syndrome: a case report

et al. 2020

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Background: Li-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome. Case presentation: This is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. When the patient was 41 years old, her seven-year-old daughter was found to have an astrocytoma and a germline TP53 mutation. While undergoing surveillance with 68 Gallium-DOTATATE positron emission tomography/computed tomography for her PNET, the patient was found to have a large choroid plexus papilloma in her right temporal lobe. She underwent genetic counseling and testing that identified a germline pathogenic variant in TP53, leading to the diagnosis of Li-Fraumeni syndrome. Her PNET had a hemizygous pathogenic TP53 mutation with loss of the wild-type alternate allele, consistent with loss of heterozygosity and the two-hit hypothesis. She was enrolled in a Li-Fraumeni syndrome protocol and continues surveillance screening with our service. Conclusions: This is the first PNET reported in association with Li-Fraumeni syndrome. Pancreatic cancer risk is elevated in this syndrome, and our case highlights the need for vigilance in screening for pancreatic neoplasms in these patients.

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“…Recent studies have shown heterogeneous AKT1 variants, including in-frame duplications in sclerosing pneumocytoma -remarkably, 93% and 100% of two cohorts of affected individuals had AKT1 variants (Yeh et al 2019). An atypical AKT1 p.(Arg23Gln) variant was observed in two neuroendocrine tumors, although causality was not established (Park et al 2019). Finally, one individual with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion gene comprising the LAMTOR1 and AKT1 genes (Slotkin et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Allelic heterogeneity of Proteus syndrome

Buser

Lindhurst

Kondolf

et al. 2020

Cold Spring Harb Mol Case Stud

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Proteus syndrome is mosaic disorder that can cause progressive postnatal overgrowth of nearly any organ or tissue. To date, Proteus syndrome has been exclusively associated with the mosaic c.49G>A p.(Glu17Lys) pathogenic variant in AKT1, a variant that is also present in many cancers. Here we describe an individual with severe Proteus syndrome who died at 7 ½ years of age from combined parenchymal and restrictive pulmonary disease. Remarkably, this individual was found to harbor a mosaic c.49_50delinsAG p.(Glu17Arg) variant in AKT1 at a variant allele fraction that ranged from <0.01 to 0.46 in fibroblasts established from an overgrown digit. This variant was demonstrated to be constitutively activating by phosphorylation of AKT(S473). These data document allelic heterogeneity for Proteus syndrome. We recommend that individuals with a potential clinical diagnosis of Proteus syndrome who are negative for the p.(Glu17Lys) variant be tested for other variants in AKT1.

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Targeted next-generation sequencing of well-differentiated rectal, gastric, and appendiceal neuroendocrine tumors to identify potential targets

Cited by 30 publications

References 32 publications

Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

Label-Free Identification of Early Gastrointestinal Neuroendocrine Tumors via Biomedical Multiphoton Microscopy and Automatic Image Analysis

The first pancreatic neuroendocrine tumor in Li-Fraumeni syndrome: a case report

Allelic heterogeneity of Proteus syndrome

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