Change search
ReferencesLink to record
Permanent link

Direct link
Next-generation sequencing of the basal cell carcinoma miRNome and a description of novel microRNA candidates under neoadjuvant vismodegib therapy: an integrative molecular and surgical case study
Show others and affiliations
Number of Authors: 8
2016 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 2, 332-338 p.Article in journal (Refereed) Published
Abstract [en]

Background: MicroRNAs (miRNAs) have been identified as key players in posttranscriptional gene regulation and have a significant impact on basal cell carcinoma (BCC) development. The Sonic hedgehog pathway inhibitor vismodegib has been approved for oral therapy of metastatic or advanced BCC. Here, a high-throughput miRNA sequencing analysis was carried out to identify differentially expressed miRNAs and possible novel miRNA candidates in vismodegib-treated BCC tissue. Additionally, we described our surgical experience with neoadjuvant oral vismodegib therapy. Patients and methods: A punch biopsy (4 mm) from a patient with an extensive cranial BCC under oral vismodegib therapy and a corresponding nonlesional epithelial skin biopsy were harvested. Total RNA was isolated, after which a sequencing cDNA library was prepared, and cluster generation was carried out, which was followed by an ultra-high-throughput miRNA sequencing analysis to indicate the read number of miRNA expression based on miRBase 21. In addition to the identification of differentially expressed miRNAs from RNA sequencing data, additional novel miRNA candidates were determined with a tool for identifying new miRNA sequences (miRDeep2). Results: We identified 33 up-regulated miRNAs (fold change >= 2) and 39 potentially new miRNA candidates (miRDeep scores 0-43.6). A manual sequence analysis of the miRNA candidates on the genomic locus of chromosome 1 with provisional IDs of chr1_1913 and chr1_421 was further carried out and rated as promising (chr1_1913) and borderline (chr1_421). Histopathology revealed skip lesions in clinically healthy appearing skin at the tumor margins, which were the cause of seven re-excisions by micrographic controlled surgery to achieve tumor-free margins. Conclusion: miRNA sequencing revealed novel miRNA candidates that need to be further confirmed in functional Dicer knockout studies. Clinically, on the basis of our surgical experience described here, neoadjuvant vismodegib therapy in BCC appears to impede histopathologic evaluations with effects on surgical therapy. Thus, larger studies are necessary, but are not preferable at this time if other options are available.

Place, publisher, year, edition, pages
2016. Vol. 27, no 2, 332-338 p.
Keyword [en]
miRNAs, basal cell carcinoma, noncoding RNAs, next-generation sequencing
National Category
Bioinformatics and Systems Biology Genetics Cancer and Oncology
Identifiers
URN: urn:nbn:se:su:diva-128195DOI: 10.1093/annonc/mdv551ISI: 000370199100020PubMedID: 26578727OAI: oai:DiVA.org:su-128195DiVA: diva2:914015
Available from: 2016-03-23 Created: 2016-03-21 Last updated: 2016-03-23Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Friedländer, Marc R.
By organisation
Department of Molecular Biosciences, The Wenner-Gren InstituteScience for Life Laboratory (SciLifeLab)
In the same journal
Annals of Oncology
Bioinformatics and Systems BiologyGeneticsCancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 13 hits
ReferencesLink to record
Permanent link

Direct link