Whole-exome sequencing identifies recurrent AKT1 mutations in sclerosing hemangioma of lung.

Pulmonary sclerosing hemangioma (PSH) is a benign tumor with two cell populations (epithelial and stromal cells), for which genomic profiles remain unknown. We conducted exome sequencing of 44 PSHs and identified recurrent somatic mutations of AKT1 (43.2%) and ß-catenin (4.5%). We used a second subset of 24 PSHs to confirm the high frequency of AKT1 mutations (overall 31/68, 45.6%; p.E17K, 33.8%) and recurrent ß-catenin mutations (overall 3 of 68, 4.4%). Of the PSHs without AKT1 mutations, two exhibited AKT1 copy gain. AKT1 mutations existed in both epithelial and stromal cells. In two separate PSHs from one patient, we observed two different AKT1 mutations, indicating they were not disseminated but independent arising tumors. Because the AKT1 mutations were not found to co-occur with ß-catenin mutations (or any other known driver alterations) in any of the PSHs studied, we speculate that this may be the single-most common driver alteration to develop PSHs. Our study revealed genomic differences between PSHs and lung adenocarcinomas, including a high rate of AKT1 mutation in PSHs. These genomic features of PSH identified in the present study provide clues to understanding the biology of PSH and for differential genomic diagnosis of lung tumors.

Early Bone Formation at a Femur Defect Using CGF and PRF Grafts in Adult Dogs: A Comparative Study.

PURPOSE: The purpose of this study was to compare the predictability of new bone formation using an autologous concentrated growth factor (CGF) graft alone and platelet graft alone. MATERIALS AND METHODS: Four bony defects of 8 mm were formed, and 3.7- × 10-mm implants were placed in the right femur. The platelet-rich fibrin (PRF), CGF, and synthetic bone were grafted to the bone defect area. Enzyme linked immunosorbent assay quantitative analysis and microscopic analysis of the fibrinogen structure were performed. RESULTS: At 4 weeks, the comparisons of each experimental group showed a significant difference between the CGF group and the synthetic bone graft group. When comparing the CGF and allograft material groups, the allograft group showed significantly more new bone formation. In the case of vascular endothelial growth factor, CGF had 1.5 times more than PRF. CGF showed a fibrinogen structure with a constant diameter. CONCLUSION: When applied to a clinical case, CGF is predicted to show better results than PRF.

Three-dimensional volumetric analysis after sinus grafts.

PURPOSE: The purpose of this study was to evaluate the augmentation volume of a sinus graft according to the time and graft materials based on cone-beam computed tomography (CBCT) scans and to assess efficacy of a bioabsorbable membrane. METHODS: Fourteen patients were investigated, and volumetric analysis was performed using OnDemand 3DTM software (Cybermed, Seoul, Korea). CBCT scans were performed on patients before surgery, immediately after surgery, 6 months after surgery, and 1 year after surgery. Following this analysis, the volumetric data were compared with the actual grafted volumes. Bioabsorbable membranes were used in all patients to promote the protection of sinus membranes and to guide bone regeneration. RESULTS: Overall, the average percent volume of graft material that remained 6 months after implantation was 82.0%, and the average percent volume of graft material that remained 1 year after surgery was 60.4%. These reductions in the volume of graft material from immediately after surgery until 6 months or 1 year after surgery were shown to be statistically significant (P = 0.002 and P < 0.001, respectively). CONCLUSION: The slight differences observed among the data indicate that volumetric analysis performed using CBCT can provide highly accurate data. A significant difference was observed in volumetric change over time, but no significant differences were observed between materials. No significant relationship was observed between the resorption of grafted bone and the success rate.

Mini-plate removal in maxillofacial trauma patients during a five-year retrospective study.

OBJECTIVES: The purpose of this study was to analyze the incidence of indications for the removal of mini-plates over a five-year period in maxillofacial trauma patients. MATERIALS AND METHODS: The medical records of 530 patients who underwent treatment with mini-plate fixation after maxillofacial trauma were reviewed for a five-year period (May 2007 to May 2012). Patients were evaluated concerning the number of mini-plates removed, age and gender distributions, time between insertion and removal, indication for removal, and site of removal. RESULTS: The plates of 120 patients were removed (26 females and 94 males). The removal rate was 22.6%. The most frequent indication for removal was patient demand (81.7%), followed by tooth extraction (7.5%), and pain (3.3%). The most frequent removal site was the mandible (95.0%). CONCLUSION: The number of mini-plates removed was small, and the most common indication for removal was patient demand. There is no evidence to support a recommendation for the routine removal of titanium mini-plates.

Mutational burdens and evolutionary ages of thyroid follicular adenoma are comparable to those of follicular carcinoma.

Follicular thyroid adenoma (FTA) precedes follicular thyroid carcinoma (FTC) by definition with a favorable prognosis compared to FTC. However, the genetic mechanism of FTA to FTC progression remains unknown. For this, it is required to disclose FTA and FTC genomes in mutational and evolutionary perspectives. We performed whole-exome sequencing and copy number profiling of 14 FTAs and 13 FTCs, which exhibited previously-known gene mutations (NRAS, HRAS, BRAF, TSHR and EIF1AX) and copy number alterations (CNAs) (22q loss and 1q gain) in follicular tumors. In addition, we found eleven potential cancer-related genes with mutations (EZH1, SPOP, NF1, TCF12, IGF2BP3, KMT2C, CNOT1, BRIP1, KDM5C, STAG2 and MAP4K3) that have not been reported in thyroid follicular tumors. Of note, FTA genomes showed comparable levels of mutations to FTC in terms of the number, sequence composition and functional consequences (potential driver mutations) of mutations. Analyses of evolutionary ages using somatic mutations as molecular clocks further identified that FTA genomes were as old as FTC genomes. Whole-transcriptome sequencing did not find any gene fusions with potential significance. Our data indicate that FTA genomes may be as old as FTC genomes, thus suggesting that follicular thyroid tumor genomes during the transition from FTA to FTC may stand stable at genomic levels in contrast to the discernable changes at pathologic and clinical levels. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful for the molecular diagnosis and therapeutics of follicular tumor patients.