Are patients with encephalocraniocutaneous lipomatosis at increased risk of developing low-grade gliomas?

Cancer-prone genetic disorders are responsible for brain tumors in a considerable proportion of children. Additionally, rare genetic syndromes associated to cancer development may potentially disclose genetic mechanisms related to oncogenesis. We describe two pediatric patients with encephalocraniocutaneous lipomatosis (ECCL), a very rare genetic syndrome with around 60 reported cases, which developed low-grade astrocytoma at 3 and 12 years of age. Patients with ECCL seem to be at risk of benign forms of osseous tumors such as ossifying fibromas, odontomas, and osteomas. The association between brain tumor and ECCL was previously reported only once, in a pediatric case of a mixed neuronal-glial histology. Whether ECCL may be a genetic condition of predisposing brain tumor in children strongly needs to be addressed.

Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.