Screening of potential novel candidate genes in schwannomatosis patients

Perez‐Becerril, Cristina; Wallace, Andrew; Schlecht, Hélene; Bowers, Naomi L.; Smith, Philip T.; Gokhale, Carolyn; Eaton, Helen; Charlton, Chris; Robinson, Rachel; Charlton, Ruth; Evans, D Gareth; Smith, Miriam J.

doi:10.1002/humu.24424

Cited by 4 publications

(2 citation statements)

References 70 publications

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“…LZTR1 had been studied mostly with respect to their functions in the nervous system, such as schwanmomatosis [ 9 ], autism [ 10 ], and Noonan syndrome [ 11 , 12 ]. However, in 2017, Cancer Genome Atlas Research Network published the results of the comprehensive and integrative genomic characterization in hepatocellular carcinoma (HCC), and they found that LZTR1 was the significantly mutated gene in HCC [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer

Zhou

Ying

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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The elucidation of the action site, mechanism of Leucine-Zipper-like Transcription Regulator-1 (LZTR1) and its relationship with RAS-MAPK signaling pathway attracts more and more scholars to focus on the researches of LZTR1 and its role in tumorigenesis. However, there was no pan-cancer analysis between LZTR1 and human tumors reported before. Therefore, we are the first to investigate the potential oncogenic roles of LZTR1 across all tumor types based on the datasets of TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus). LZTR1 plays a double-edged role in tumor development and prognosis. We found that the high expression of LZTR1 brings better outcomes in esophageal carcinoma (ESCA) and head and neck squamous cell carcinoma (HNSC) but brings worth outcomes in uveal melanoma (UVM), adrenocortical carcinoma (ACC), liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Moreover, the expression of LZTR1 also strongly associated with pathological in ACC and bladder urothelial carcinoma (BLCA). We also found that the LZTR1 expression was associated with some immune cell infiltration including endothelial cells, regulatory T cells (Tregs), T cell CD8+, natural killer cells (NK cell), macrophages, neutrophil granulocyte, and cancer-associated fibroblasts in different cancers. Missense mutation in LZTR1 was detected in most cancers from TCGA datasets. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Body (GO) method was used to explain the pathogenesis of LZTR1. Our pan-cancer study provides a relatively comprehensive understanding of the carcinogenic role of LZTR1 in human tumors.

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Section: Introductionmentioning

confidence: 99%

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer

Zhou

Ying

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…2. Of note, SMARCA4- [6] and DGCR8- [7,8] schwannomatosis represent two recent forms of schwannomatosis, without any specific clinical features, and might constitute rare events [9].…”

Section: Key Pointsmentioning

confidence: 99%

Schwannomatosis: a Realm Reborn: year one

Planet,

Kalamarides,

Peyre

2023

Current Opinion in Oncology

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Purpose of review In 2022, an international consensus recommendation revised the nomenclature for neurofibromatosis type 2 (NF2) and Schwannomatosis (SWN), now grouped under the umbrella term Schwannomatosis, and defined new diagnostic criteria. Recent findings This review describes the molecular criteria for diagnosis of schwannomatosis and the subsequent diagnosis strategy, while setting out the most recent advances in our understanding of the natural history, pathology, molecular biology and treatment of schwannomatosis-associated tumors, including schwannomas, meningiomas and ependymomas. Summary Somatic mutation screening should become a new standard for the diagnosis of NF2-, LTZTR1-, SMARCB1- and 22q-schwannomatosis to discriminate those conditions. Constitutional events in NF2-Schwannomatosis have a major influence on disease severity and justifiably motivate ongoing efforts on gene replacement therapy research. On the other hand, underlying mechanisms of disease severity and associated pain remain largely unknown in non-NF2-SWN and independent of germline mutation. Research efforts therefore focus on pain relief in ongoing trials and the discovery of new molecular mechanisms underlying schwannoma tumorigenesis/pain/neuropathies.

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Screening of potential novel candidate genes in schwannomatosis patients

et al. 2022

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Schwannomatosis comprises a group of hereditary tumor predisposition syndromes characterized by, usually benign, multiple nerve sheath tumors, which frequently cause severe pain that does not typically respond to drug treatments. The most common schwannomatosis‐associated gene is NF2, but SMARCB1 and LZTR1 are also associated. There are still many cases in which no pathogenic variants (PVs) have been identified, suggesting the existence of as yet unidentified genetic risk factors. In this study, we performed extended genetic screening of 75 unrelated schwannomatosis patients without identified germline PVs in NF2, LZTR1, or SMARCB1. Screening of the coding region of DGCR8, COQ6, CDKN2A, and CDKN2B was carried out, based on previous reports that point to these genes as potential candidate genes for schwannomatosis. Deletions or duplications in CDKN2A, CDKN2B, and adjacent chromosome 9 region were assessed by multiplex ligation‐dependent probe amplification analysis. Sequencing analysis of a patient with multiple schwannomas and melanomas identified a novel duplication in the coding region of CDKN2A, disrupting both p14ARF and p16INK4a. Our results suggest that none of these genes are major contributors to schwannomatosis risk but the possibility remains that they may have a role in more complex mechanisms for tumor predisposition.

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Screening of potential novel candidate genes in schwannomatosis patients

Cited by 4 publications

References 70 publications

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer

A Comprehensive Pan-Cancer Analysis of the Tumorigenic Effect of Leucine-Zipper-Like Transcription Regulator (LZTR1) in Human Cancer

Schwannomatosis: a Realm Reborn: year one

Screening of potential novel candidate genes in schwannomatosis patients

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