Application of patient derived liver cancer cell lines for phenotypic characterization and therapeutic target identification

ANKRD26-RET - A novel gene fusion involving RET in papillary thyroid carcinoma

Abstract Background Rearrangements of RET are drivers of oncogenesis, traceable in different cancer types as papillary thyroid carcinoma (PTC), non-small cell lung cancer, colorectal or breast cancer. Anchored multiplex PCR based next-generation sequencing (NGS) can detect RET rearrangements involving previously unknown partner genes. Methods A sample of PTC underwent NGS, following detection of RET rearrangement by fluorescence in situ hybridization. Expression analysis of ANKRD26 and RET was performed for the tumor harboring ANKRD26-RET, for corresponding normal thyroid tissue and PTC tumors with representative genetic alterations (BRAFV600E, CCDC6-RET), complemented by a comparative sear…

Novel rearrangements involving the RET gene in papillary thyroid carcinoma.

Abstract Background In the field of gene fusions driving tumorigenesis in papillary thyroid carcinoma (PTC), rearrangement of the proto-oncogene RET is the most frequent alteration. Apart from the most common rearrangement of RET to CCDC6, more than 15 partner genes are yet reported. The landscape of RET rearrangements in PTC (“RET-PTC”) can notably be enlarged by modern targeted next-generation sequencing, indicating similarities between oncogenic pathways in other cancer types with identical genetic alterations. Methods Targeted next-generation sequencing was performed for two cases of BRAF-wild type PTC with confirmation of the results by Sanger sequencing. A “UniProt” database research …

Cluster of differentiation 44 promotes osteosarcoma progression in mice lacking the tumor suppressor Merlin.

Merlin is a versatile tumor suppressor protein encoded by the NF2 gene. Several lines of evidence suggest that Merlin exerts its tumor suppressor activity, at least in part, by forming an inhibitory complex with cluster of differentiation 44 (CD44). Consistently, numerous NF2 mutations in cancer patients are predicted to perturb the interaction of Merlin with CD44. We hypothesized that disruption of the Merlin-CD44 complex through loss of Merlin, unleashes putative tumor- or metastasis-promoting functions of CD44. To evaluate the relevance of the Merlin-CD44 interaction in vivo, we compared tumor growth and progression in Cd44-positive and Cd44-negative Nf2-mutant mice. Heterozygous Nf2-mut…

Application of Patient-Derived Liver Cancer Cells in Personalized Treatment Approach: Phenotypic Characterization and Therapeutic Target Identification

Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification.

Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors. Time course analyses of transcriptomic and genomic changes were…