Gene Methylation Profiling in Sinonasal Adenocarcinoma and Squamous Cell Carcinoma

Costales, María; López-Hernández, Alejandro; García‐Inclán, Cristina; Vivanco, Blanca; López, Fernándo; Llorente, José Luís; Hermsen, Mario

doi:10.1177/0194599816654139

Cited by 14 publications

(15 citation statements)

References 47 publications

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“…In addition, with the exception of MAPK/ERK pathway mutations that all occurred in papillary and colonic type tumors, we were unable to find relevant differences between the four ITAC histological subtypes. This seems to suggest that ITAC is a genetically homogeneous group of tumors, which contrasts with previous claims that mucinous type ITAC stands apart from the other subtypes in terms of TP53 mutation and p53 overexpression, nuclear b-catenin and E-cadherin expression, gene promotor hypermethylation and chromosomal copy number alteration profile 22 , 35 , 53 – 55 . Finally, mutated pathways MAPK/ERK, DNA repair, WNT and PI3K did not correlate to tumor stage, overall or disease-specific survival.…”

Section: Discussioncontrasting

confidence: 96%

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

Sánchez-Fernández

Riobello

Costales

et al. 2021

Sci Rep

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Intestinal-type sinonasal adenocarcinoma (ITAC) is a rare tumor carrying poor prognosis and needing new treatment options. The aim of this study was to identify actionable gene mutations that can guide new personalized target-specific therapies in ITAC patients. A series of 48 tumor and 27 corresponding germline DNA samples were analyzed by next generation sequencing using a panel of 120 genes. In total, 223 sequence variants were found in 70 genes. Matched tumor/germline comparison in 27 cases revealed that 57% were in fact germline variants. In 20 of these 27 cases, 58 somatic variants in 33 different genes were identified, the most frequent being PIK3CA (5 cases), APC and ATM (4 cases), and KRAS, NF1, LRP1B and BRCA1 (3 cases). Many of the somatic gene variants affected PI3K, MAPK/ERK, WNT and DNA repair signaling pathways, although not in a mutually exclusive manner. None of the alterations were related to histological ITAC subtype, tumor stage or survival. Our data showed that thorough interpretation of somatic mutations requires sequencing analysis of the corresponding germline DNA. Potentially actionable somatic mutations were found in 20 of 27 cases, 8 of which being biomarkers of FDA-approved targeted therapies. Our data implicate new possibilities for personalized treatment of ITAC patients.

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Section: Discussioncontrasting

confidence: 96%

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

Sánchez-Fernández

Riobello

Costales

et al. 2021

Sci Rep

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“…papillary and mucinous), p53 status and intracranial invasion. A previous study assessing gene promoter methylation demonstrated a pattern, which differentiated SNSCC from ITAC [66]. Here, the authors found recurrent promoter methylation in ITAC of the genes CDH13, ESR1, APC, TIMP3, CASP8, HIC1 and RASSF1.…”

Section: Novel Biomarkers In Sinonasal Adenocarcinomasupporting

confidence: 53%

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside

2020

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Purpose of Review Sinonasal cancers are a heterogenous group of rare cancers for which histopathological diagnosis can be very challenging and treatment options are limited for advanced disease in particular. Here, we review the candidacy of novel diagnostic and prognostic biomarkers, and therapeutic targets for sinonasal cancers. Recent Findings Molecular multidimensional analyses of sinonasal cancers have been lagging behind other major cancers, but there are numerous publications describing the discovery of novel candidate biomarkers, e.g. the methylation classifier, originally developed for brain cancers, and gene expression panels for the prediction of response to induction chemotherapy in sinonasal undifferentiated carcinoma. The most promising biomarkers are summarized and discussed further with regard to their clinical applicability and future potential. Summary Many of the described novel biomarkers for sinonasal cancers will eventually overcome the pitfalls associated with the frequently non-specific immunohistological tests. With comprehensive, multidimensional molecular testing of these tumours in collaborative consortia projects, our better understanding of the molecular mechanisms of sinonasal cancers and their carcinogenesis will determine the most useful diagnostic and prognostic biomarkers, allow stringent multi-institutional validation and guide trials on targeted therapies.

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“…Epigenetic studies on sinonasal papillomas and carcinomas are extremely rare and only focused on tumour‐suppressor gene hypermethylation . Taken together all these studies suggest the importance to clarify the role of epigenetic aberrations in the pathogenesis of sinonasal papillomas and SCCs.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a recent case–control study found a significantly increased risk among subjects previously exposed to organic solvents, welding fumes and nickel compounds, extending previous observations indicating an unusually high proportion of cases in those employed in the steel industry and in manufacturing . Although in vivo and in vitro studies have observed an association between exposure to chemical compounds such as polycyclic aromatic hydrocarbon and benzene and the presence of alterations of DNA methylation in healthy and transformed cells, globally in sinonasal tumours epigenetic studies on aberrant locus‐specific hypermethylation are currently scanty and on DNA hypomethylation are still missing.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal‐inverted papilloma to squamous cell carcinoma

Sahnane

Ottini

Turri‐Zanoni

et al. 2018

Intl Journal of Cancer

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Different risk factors are suspected to be involved in malignant transformation of sinonasal papillomas and include HPV infection, tobacco smoking, occupational exposure, EGFR/KRAS mutations and DNA methylation alterations. In our study, 25 inverted sinonasal papillomas (ISPs), 5 oncocytic sinonasal papillomas (OSP) and 35 squamous cell carcinomas (SCCs) from 54 patients were genotyped for 10 genes involved in EGFR signalling. HPV-DNA detection was performed by in-situ hybridisation and LINE-1 methylation was quantitatively determined by bisulphite-pyrosequencing. High-risk HPV was observed only in 13% of ISP-associated SCC and in 8% of de novo-SCC patients. EGFR mutations occurred in 72% of ISPs, 30% of ISPassociated SCCs and 17% of de novo-SCCs. At 5-year follow-up, SCC arose in only 30% (6/20) of patients with EGFR-mutated ISPs compared to 76% (13/17) of patients with EGFR-wild-type ISP (p = 0.0044). LINE-1 hypomethylation significantly increased from papilloma/early stage SCC to advanced stage SCC (p = 0.03) and was associated with occupational exposure (p = 0.01) and worse prognosis (p = 0.09). In conclusion, our results suggest that a small subset of these tumours could be related to HPV infection; EGFR mutations characterise those ISPs with a lower risk of developing into SCC; LINE-1 hypomethylation is associated with occupational exposure and could identify more aggressive nasal SCC.Additional Supporting Information may be found in the online version of this article. Conflict of interest: The authors declare no conflict of interest.

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Gene Methylation Profiling in Sinonasal Adenocarcinoma and Squamous Cell Carcinoma

Cited by 14 publications

References 47 publications

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

Next-generation sequencing for identification of actionable gene mutations in intestinal-type sinonasal adenocarcinoma

Novel Biomarkers in Sinonasal Cancers: from Bench to Bedside

Comprehensive analysis of HPV infection, EGFR exon 20 mutations and LINE1 hypomethylation as risk factors for malignant transformation of sinonasal‐inverted papilloma to squamous cell carcinoma

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