Example of Summary Table for Evaluation of Percent Agreement.

<p>In the table:</p><p><i>a</i> = number of specimens tested positive by both Method 1 and Method 2.</p><p><i>b</i> = number of specimens tested positive by Method 1 and negative by Method 2.</p><p><i>c</i> = number of specimens tested negative by Method 1 and positive Method 2.</p><p><i>d</i> = number of specimens tested negative by both Method 1 and Method 2.</p><p>The following statistics will be calculated:</p><p>•Overall Percent agreement between Methods = .</p><p>•Positive Percent Agreement between Methods = .</p><p>•Negative Percent Agreement between Methods = .</p><p>95% confidence intervals for the above percent agreements will be calculated using methods described in CLSI EP12-A, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline, 2002.</p

Methods correlation between RT-PCR test and Sanger at Site 1 and after 454 sequencing of discrepant specimens.

<p>CI = confidence interval; MD = mutation detected; MND = mutation not detected.</p>*<p>One sample subsequently confirmed as V600E by 454; Two samples subsequently confirmed as V600K;</p>†<p>Subsequently confirmed as non-V600E/wild-type by 454.</p

Distribution of pathological characteristics.

<p>NA = Not applicable.</p>a<p>Low = <10%; high = ≥10%.</p>b<p>Low = <50%; high = ≥50%.</p

Invalid test rates.

*<p>Retesting was permitted according to the manufacturer’s or procedure’s instructions as follows: RT-PCR test: <50% tumour content, insufficient DNA concentration, or invalid initial test result; Sanger: no PCR amplification or difficult sequence interpretation; FA test: fluorescence signal too strong, background noise, extra peaks that did not match any peaks from controls, or small mutation peaks that were difficult to identify as mutation signals.</p>†<p>The same sample was invalid when tested at the two sites.</p

Key milestones in the co-development of vemurafenib and the cobas® 4800 BRAF V600 Mutation Test.

<p>Phases of companion diagnostic (CoDx) development in green, drug (Rx) development in blue. IDE = Investigational Device Exemption; IND = Investigational New Drug Application; MAA = Marketing Authorisation Application; NDA = New Drug Application; PMA = Premarket Approval Application; RMS = Roche Molecular Systems, Inc.</p

Methods correlation between RT-PCR test and FA test sequencing at Site 2 and after 454 sequencing of discrepant specimens.

<p>CI = confidence interval; MD = mutation detected; MND = mutation not detected.</p>*<p>Seven samples were reported as wild type by FA test and ‘mutation detected’ by RT-PCR test of which four were subsequently found to be V600E by 454, and three to be V600K. One sample was reported as V600G by FA test and ‘mutation detected’ by the RT-PCR test and was subsequently found to be V600K by 454.</p>†<p>Twelve samples subsequently reported as wild type, three as V600E2, and one as V600R by 454.</p

Study design and specimen selection.

<p>FFPET = formalin-fixed paraffin-embedded tissue. * Low tumor content (<50%); high levels of necrosis (≥50%); significant pigmentation (<10%); or non-V600E mutations.</p

Relative quantification of deregulated microRNAs in the independent validation cohort.

<p>Expression of deregulated miRNAs was evaluated in the validation cohort. MicroRNA expression levels were determined in tumor and paired normal lung tissue of lung cancer patients and relative expression by histological subtype was assessed. Median ΔΔCt values were determined in nine miRNAs in patients with adenocarcinoma versus SCC. Data derived from RT-qPCR are presented as 2^−ΔΔCt values. <i>P</i> value below 0.05 was considered significant.</p

Summary of patients’ characteristics of the validation cohort.

<p>Continuous variables are expressed as median [interquartile range (IQR)] and categorical ones as number of cases (%).</p

Spearman’s correlation between miRNA and target gene expression in patients with lung adenocarcinoma or squamous cell carcinoma.

<p>Expression of the 6 validated miRNAs and that of their putative target genes was measured in each patient in the validation cohort. The significance of the inverse association between each of these miRNA/mRNA couples was assessed by the Spearman’s correlation coefficient. P values less than 0.05 were considered statistically significant. A) Relationships between <i>ABCC3</i>, <i>MUC1</i> and <i>CEACAM6</i> with miR-149. B) Relationships between <i>ACSL5</i> and <i>CEACAM6</i> with miR-205. C) Relationship between <i>TMEM45B</i> and miR-378. D) Relationship between <i>TMEM45B</i> and miR-422a. E) Relationship between <i>CEACAM6</i> and miR-7018. F) Relationship between <i>KRT6A</i> and miR-miR-175.</p