Additional file 2: Figure S2. of Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas

Cladogram depicting phylogenetic relationship of taxa identified as significantly different (p < 0.05) by Wilcoxon signed-rank testing in tumor relative to adjacent histologically normal tissue prior to correction for FDR. Each concentric ring of nodes represents a taxonomic rank, starting with kingdom at the very center. Moving outwards, the rings represent phylum, class, order, family, and genus. Nodes highlighted in orange are increased in tumor relative to normal samples. Nodes highlighted in blue are increased in normal relative to tumor samples. (TIFF 2213 kb

Additional file 1: Figure S1. of Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas

Overall oral microbiomic diversity of patient samples as represented by PCoA of (A) weighted and (B) unweighted UniFrac distances. Each point represents a single tumor (orange) or normal (blue) sample, with connecting lines delineating a tumor/normal pair from the same patient. (TIFF 1177 kb

A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing Is Proposed on the Basis of a Prospective Study of 3042 Probands

Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome are allelic, defined by germline PTEN mutations, and collectively referred to as PTEN hamartoma tumor syndrome. To date, there are no existing criteria based on large prospective patient cohorts to select patients for PTEN mutation testing. To address these issues, we conducted a multicenter prospective study in which 3042 probands satisfying relaxed CS clinical criteria were accrued. PTEN mutation scanning, including promoter and large deletion analysis, was performed for all subjects. Pathogenic mutations were identified in 290 individuals (9.5%). To evaluate clinical phenotype and PTEN genotype against protein expression, we performed immunoblotting (PTEN, P-AKT1, P-MAPK1/2) for a patient subset (n = 423). In order to obtain an individualized estimation of pretest probability of germline PTEN mutation, we developed an optimized clinical practice model to identify adult and pediatric patients. For adults, a semiquantitative score—the Cleveland Clinic (CC) score—resulted in a well-calibrated estimation of pretest probability of PTEN status. Overall, decreased PTEN protein expression correlated with PTEN mutation status; decreasing PTEN protein expression correlated with increasing CC score (p < 0.001), but not with the National Comprehensive Cancer Network (NCCN) criteria (p = 0.11). For pediatric patients, we identified highly sensitive criteria to guide PTEN mutation testing, with phenotypic features distinct from the adult setting. Our model improved sensitivity and positive predictive value for germline PTEN mutation relative to the NCCN 2010 criteria in both cohorts. We present the first evidence-based clinical practice model to select patients for genetics referral and PTEN mutation testing, further supported biologically by protein correlation