Evaluation of the correlation betweenKRASmutated allele frequency and pathologist tumorous nuclei percentage assessment in colorectal cancer suggests a role for zygosity status

Abstract

<jats:p>Evaluation of molecular tumour heterogeneity relies on the tumorous nuclei percentage (TNP) assessment by a pathologist, which has been criticised for being inaccurate and suffering from interobserver variability. Based on the ‘Big Bang theory’ which states that <jats:italic>KRAS</jats:italic> mutation in colorectal cancer is mostly homogeneous, we investigated this issue by performing a critical analysis of the correlation of the <jats:italic>KRAS</jats:italic> mutant allele fraction with the TNP in 99 colorectal tumour samples with a positive <jats:italic>KRAS</jats:italic> mutation status as determined by next-generation sequencing. Our results yield indirect evidence that the KRAS zygosity status influences the correlation between these parameters and we show that a well-trained pathologist is indeed capable of accurately assessing TNP. Our findings indicate that tumour zygosity, a feature which has largely been neglected until now, should be taken into account in future studies on (colorectal) molecular tumour heterogeneity.</jats:p>

Form-Vessel Classification of Cholangioscopy Findings to Diagnose Biliary Tract Carcinoma’s Superficial Spread

“…The VAF, also known as the mutant allele frequency, indicates tumor cellularity from extracted DNA. The VAF has been used to predict the degree of malignancy [23] and the reactivity to drugs [27] in certain tumors. Thus, we used the VAFs of biopsied bile duct specimens to classify the degree of malignancy.…”

“…Of note, targeted deep sequencing has a high sensitivity in detecting multiple gene mutations. The variant allele frequency (VAF) of genes reflect the fraction of tumor cells per sample and can be used to determine the tumor grade [23].…”