Genetic characterization of basal cell carcinoma in correlation to circulating tumor cell detection

  • Viktoria Binder

Studienabschlussarbeit: Masterarbeit

Abstract

Basal cell carcinoma (BCC) is the most frequent epithelial skin cancer in the Caucasian population. Over the course of the research project “Liquid biopsy and molecular genetics for monitoring and early detection of progression in melanoma patients”, circulating tumor cells (CTCs) were detected in BCC patients. Given that there is currently no comparable literature on the correlation between BCCs and CTCs, the question arises as to why cells which are associated with metastasis are present in patients with BCCs, which normally do not metastasize. Therefore, this thesis deals with the detailed genetic characterization of BCC tissue samples to evaluate possible correlations to the presence and quantity of CTCs. In order to do so, a cohort of 72 patients with BCC was recruited. Magnetic beads and a recombinant protein, VAR2CSA, which can bind to the oncofetal chondroitin sulfate on the surface of the tumor cells, were added to the patient’s blood samples, followed by immunofluorescent staining to detect CTCs. In addition, tissue samples of 16 patients of the cohort were genetically analyzed using the TruSight Oncology 500 assay (TSO 500, Illumina®), which covers 523 genes. The resulting variants were classified according to the ACGS best practice guideline. In total, 12.16 % of all patients presented clear CTCs and all sequenced BCC tissue samples showed likely pathogenic or pathogenic variants affecting the Hedgehog signaling pathway, including PTCH1 with 75 % and SMO with 25 %, which were determined to be mutually exclusive in all samples. Additionally, the gain of function variant with the amino acid change Leu412Phe, a known somatic BCC driver mutation, was found in all SMO positive patients. Overall, likely pathogenic and pathogenic PTCH1 variants were present in samples with positive, slightly positive and negative CTC detection, whereas SMO mutations were only present in samples with positive and slightly positive CTC detection. In addition to the genes involved in the Hedgehog pathway, other cancer-associated genes harbored variants labelled as likely pathogenic or pathogenic, including for example the tumor suppressor gene TP53 with 69 % and MYCN with 31 %. Overall, no significant differences were detected between CTC positive, slightly positive and negative samples regarding the number of total variants, variants of uncertain significance and pathogenic variants. However, a correlation between pathogenic SMO variants and positive and slightly positive CTC detection in BCC patients can be assumed.
Datum der Bewilligung2024
OriginalspracheEnglisch
Betreuer/-inManuel Selg (Betreuer*in)

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