ZNF768 Expression Associates with High Proliferative Clinicopathological Features in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a leading cause of cancer-related deaths worldwide. Despite important recent advances, the prognosis for LUAD patients is still unfavourable, with a 5 year-survival rate close to 15%. Improving the characterization of lung tumors is important to develop alternative options for the diagnosis and the treatment of this disease. Zinc-finger protein 768 (ZNF768) is a transcription factor that was recently shown to promote proliferation and repress senescence downstream of growth factor signaling. Although ZNF768 protein levels were found to be elevated in LUAD compared to normal lung tissue, it is currently unknown whether ZNF768 expression associates with clinicopathological features in LUAD. Here, using tissue microarrays of clinical LUAD surgical specimens collected from 364 patients, we observed that high levels of ZNF768 is a common characteristic of LUAD. We show that ZNF768 protein levels correlate with high proliferative features in LUAD, including the mitotic score and Ki-67 expression. Supporting a role for ZNF768 in promoting proliferation, we report that ZNF768 depletion severely impairs proliferation in several lung cancer cell lines in vitro. A marked decrease in the expression of key proliferative genes was observed in cancer cell lines depleted from ZNF768. Altogether, our findings support a role for ZNF768 in promoting proliferation of LUAD.

Phospho-histone-H3 immunostaining for pulmonary carcinoids: impact on clinical appraisal, interobserver correlation, and diagnostic processing efficiency.

Lung carcinoid tumors are classified as either typical or atypical based on the presence of necrosis and the maximum mitotic count per 2 mm2 area. Determining the mitotic count, which is manually conducted on slides stained with hematoxylin and eosin (HE), is time-consuming and subject to high interobserver variability. The objective of this study was to test the sensitivity and specificity of a surrogate mitosis marker, phospho-histone-H3 (PHH3) immunostaining, in the processing of pulmonary carcinoids as compared with the standard HE evaluation. Carcinoid tissue blocks that were available from lung resection specimens were analyzed using HE and PHH3 stains. Two thoracic pathologists and two residents determined the mitotic count on HE and PHH3 stains in accordance with the 2015 WHO guidelines and recorded the time required to complete this task. For both methods, the interobserver agreement among raters for the mitotic count/2 mm2 was assessed by conducting intraclass correlation analyses. We found that for both pathologists and residents, the time required to determine the mitotic count using the PHH3 method was reduced compared with the traditional HE method. Furthermore, residents detected more mitoses/2 mm2 using the PHH3 stain compared with the HE method. More importantly, the PHH3 method yielded better interobserver agreement than the HE method in terms of mitoses/mm2 detection. Overall, our data confirmed that histologic assessments of carcinoid tumors using PHH3 staining provides practical benefits in terms of scoring times, mitosis detection, and reproducibility of mitotic counts. In addition, we found that the benefit was even greater for less experienced pathologists.

Correction to: Efficacy of Dabrafenib for three children with brainstem BRAFV600E positive ganglioglioma.

In the original article, the author names were published incorrectly. The names are correct in this publication.

CaPSID: a bioinformatics platform for computational pathogen sequence identification in human genomes and transcriptomes.

BACKGROUND: It is now well established that nearly 20% of human cancers are caused by infectious agents, and the list of human oncogenic pathogens will grow in the future for a variety of cancer types. Whole tumor transcriptome and genome sequencing by next-generation sequencing technologies presents an unparalleled opportunity for pathogen detection and discovery in human tissues but requires development of new genome-wide bioinformatics tools. RESULTS: Here we present CaPSID (Computational Pathogen Sequence IDentification), a comprehensive bioinformatics platform for identifying, querying and visualizing both exogenous and endogenous pathogen nucleotide sequences in tumor genomes and transcriptomes. CaPSID includes a scalable, high performance database for data storage and a web application that integrates the genome browser JBrowse. CaPSID also provides useful metrics for sequence analysis of pre-aligned BAM files, such as gene and genome coverage, and is optimized to run efficiently on multiprocessor computers with low memory usage. CONCLUSIONS: To demonstrate the usefulness and efficiency of CaPSID, we carried out a comprehensive analysis of both a simulated dataset and transcriptome samples from ovarian cancer. CaPSID correctly identified all of the human and pathogen sequences in the simulated dataset, while in the ovarian dataset CaPSID's predictions were successfully validated in vitro.

Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24.

Using a multistage genetic association approach comprising 7,480 affected individuals and 7,779 controls, we identified markers in chromosomal region 8q24 associated with colorectal cancer. In stage 1, we genotyped 99,632 SNPs in 1,257 affected individuals and 1,336 controls from Ontario. In stages 2-4, we performed serial replication studies using 4,024 affected individuals and 4,042 controls from Seattle, Newfoundland and Scotland. We identified one locus on chromosome 8q24 and another on 9p24 having combined odds ratios (OR) for stages 1-4 of 1.18 (trend; P = 1.41 x 10(-8)) and 1.14 (trend; P = 1.32 x 10(-5)), respectively. Additional analyses in 2,199 affected individuals and 2,401 controls from France and Europe supported the association at the 8q24 locus (OR = 1.16, trend; 95% confidence interval (c.i.): 1.07-1.26; P = 5.05 x 10(-4)). A summary across all seven studies at the 8q24 locus was highly significant (OR = 1.17, c.i.: 1.12-1.23; P = 3.16 x 10(-11)). This locus has also been implicated in prostate cancer.