Identification of metastasis-related genes by genomic and transcriptomic studies in murine melanoma

• Published in: Life sciences (1973) 2021-02, Vol.267, p.118922, Article 118922
• Main Authors: Kadioglu, Onat, Saeed, Mohamed E.M., Mahmoud, Nuha, Hussein Azawi, Shaymaa S., Rincic, Martina, Liehr, Thomas, Efferth, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Carcinogenesis; carcinoma; Cell Line, Tumor; Chromosomal aberrations; Chromosome aberrations; Chromosomes; Cytogenetics; DNA probes; Esophagus; Fluorescence; Fluorescence in situ hybridization; Gastric cancer; Gene sequencing; Genes; Genetic analysis; Genome - genetics; Genomics; Genomics - methods; hybridization; In Situ Hybridization, Fluorescence - methods; Melanoma; Melanoma - genetics; Melanoma, Experimental - genetics; Metastases; Metastasis; Mice; Mice, Inbred C57BL; Neoplasm Metastasis - genetics; neoplasm progression; RNA-sequencing; sequence analysis; Sequence Analysis, RNA - methods; stomach neoplasms; Transcriptome - genetics; Transcriptomics; Tumorigenesis; Tumors
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118922

We systematically characterized metastatic murine B16-F10 melanoma, a sub-line derived from murine melanoma B16-F1 cells. RNA-sequencing and network analyses (Ingenuity Pathway Analysis) were performed to identify novel potential metastasis mechanisms. Chromosomal aberrations were identified by multicolor fluorescence in situ hybridization (mFISH) using all 21 murine whole chromosome painting probes. Numerous genes were overexpressed in B16-F10 cells, some of which have been already described as being metastasis-linked. Nr5a1/sf1, a known prognostic marker for adrenal tumors, was 177-fold upregulated in B16-F10 cells compared to B16-F1 cells. Hoxb8 was 75-fold upregulated, which was previously associated with gastric cancer progression and metastasis. Ptk7, which is linked with tumorigenesis and metastasis of esophageal squamous carcinoma, was 67-fold upregulated. B16-F10 cells acquired additional chromosomal aberrations compared to B16-F1 cells, including dic(4)(pter->qter:qter->pter), +dic(6;15), +der(10)t(10;?1;16). In addition to well-known metastatic genes, numerous novel genes and genomic aberrations were identified, which may serve as targets for treatment in the future. Transcriptomic and genetic analyses in B16-F10 cells unraveled a range of novel metastasis mechanisms, which may also have important implications for future treatment strategies.