Whole-exome and targeted gene sequencing of large-cell lung carcinoma reveals recurrent mutations in the PI3K pathway.

BACKGROUND: Large cell lung carcinoma (LCLC) is an exceptionally aggressive disease with a poor prognosis. At present, little is known about the molecular pathology of LCLC. METHODS: Ultra-deep sequencing of cancer-related genes and exome sequencing were used to detect the LCLC mutational in 118 tumor-normal pairs. The cell function test was employed to confirm the potential carcinogenic mutation of PI3K pathway. RESULTS: The mutation pattern is determined by the predominance of A > C mutations. Genes with a significant non-silent mutation frequency (FDR) < 0.05) include TP53 (47.5%), EGFR (13.6%) and PTEN (12.1%). Moreover, PI3K signaling (including EGFR, FGRG4, ITGA1, ITGA5, and ITGA2B) is the most mutated pathway, influencing 61.9% (73/118) of the LCLC samples. The cell function test confirmed that the potential carcinogenic mutation of PI3K pathway had a more malignant cell function phenotype. Multivariate analysis further revealed that patients with the PI3K signaling pathway mutations have a poor prognosis (P = 0.007). CONCLUSIONS: These results initially identified frequent mutation of PI3K signaling pathways in LCLC and indicate potential targets for the treatment of this fatal type of LCLC.

[Changes of cranio-facial hard tissue after orthodontic treatment in bimaxillary protrusive patients].

OBJECTIVE: The aim of this study is to investigate the changes of hard tissue profile in anterior-posterior and vertical direction in bimaxillary protrusion patients after orthodontic treatment. METHODS: A total of 24 bimaxillary protrusion patients (male 8, female 16), aged from 11.2 to 29.0 (average 16.9 years old), were selected to be treated with standard edgewise technique consisted of 4 first premolars extraction. Cephalometrics were taken before and after treatment. The changes of hard tissue profile were studied using the computer-aid X-ray cephalometric analysis. RESULTS: 1. The length of the maxillary and the mandible increased significantly, but the anterior-posterior relationship of the maxillary and the mandible did not change significantly. 2. The anterior and posterior facial height increased significantly, but the ratio of anterior and posterior facial height and the angle of MP-FH which reflected the inclination of the mandible plane did not change significantly. 3. The height of the upper and lower first molar increased significantly along with the increase of the anterior and posterior facial height. 4. The height of the upper incisors increased significantly, but the height of the lower incisors decreased significantly. CONCLUSION: The anchorage in anterior-posterior and vertical direction were controlled preferably, the patients did not manifest disadvantageous vertical growth trend.