Figure 1.

Synchronous tumors of the aerodigestive tract possess distinct tumor biology from that of metachronous tumors. (A) Heatmap illustrating the mutational landscape of the samples derived from three distinct patients. Frequency of single nucleotide variants in tumor and adjacent normal mucosa indicate lower mutation counts in normal mucosa (M) compared to that of tumor (T) in all three patients. (B) No shared mutations were identified between the normal mucosa and synchronous tumors while merely one shared mutation was identified in metachronous tumors and mucosa. (C) Few copy number alterations are shared across the samples in both synchronous and metachronous tumors. (D) Signature 3 was common to synchronous tumors whereas Signature 4 was unique to metachronous tumors. (E) Differential modulation of signaling pathways is seen between synchronous (HN129) and metachronous (HN49) tumors via gene set enrichment analysis (GSEA). Normalized expression values are reflected in the bar charts, where p-value < 0.05 is represented with blue (down-regulated) or red (up-regulated). Our data revealed that hedgehog pathway was significantly enriched in synchronous tumors. SNV, single nucleotide variants; M, mucosa; T, tumor; Shh, sonic hedgehog.