Human UXT blocking peptide

Aims De-differentiated chordoma is an uncommon and incompletely characterised aggressive neoplasm. Only a few cases originating from the skull base have been reported. Methods and results All consecutive cases of skull-base de-differentiated chordomas treated surgically in a referral centre from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. Six cases (two male, four female; mean age at surgery = 46 years, range = 35-64), treated surgically at our institution were identified. Transformation to de-differentiated chordomas occurred after radiation therapy in three cases (mean = 13.6 years after treatment, range = 5-25), two during tumour progression, while one was de-novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumour components, corresponding to the conventional and de-differentiated portion on histological examination. The de-novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor, as five of six patients died after surgery and radiation therapy, with a mean overall survival of 29 months (range = 11-52). Conclusions Skull-base de-differentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumour de-differentiation.

LRPPRC (originally called LRP130) is an intracellular, 130-kD, leucine-rich protein that copurifies with the fibroblast growth factor receptor from liver cell extracts and has been detected in diverse multiprotein complexes from the cell membrane, cytoskeleton, and nucleus. Here we report results of a sequence homology analysis of LRPPRC and its SEC1 domain interactive partners. We found that 23 copies of tandem repeats that are similar to pentatricopeptide, tetratricopeptide, and huntingtin-elongation A subunit-TOR repeats characterize the LRPPRC sequence. The amino terminus exhibits multiple copies of leucine-rich nuclear transport signals followed by ENTH, DUF28, and SEC1 homology domains. We used the SEC1 domain to trap interactive partners expressed from a human liver cDNA library. Interactive C190RF5 (XP_038600) exhibited a strong homology to microtubule-associated proteins and a potential arginine-rich mRNA binding motif. UXT (XP_033860) exhibited a-helical properties homologous to the actin-associated spectrin repeat and L/I heptad repeats in mobile transcription factors. C6ORF34 (XP_004305) was homologous to the non-DNA-binding carboxy terminus of the Escherichia coli Rob transcription factor. CECR2 (AAK15343) exhibited a transcription factor AT-hook motif next to two bromodomains and a homology to guanylate-binding protein-1. Together these features suggest a regulatory role of LRPPRC and its SEC1 domain-interactive partners in integration of cytoskeletal networks with vesicular trafficking, nucleocytosolic shuttling, transcription, chromosome remodeling, and cytokinesis.