Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis

Authors:

Andrew M Fleming 1, Benjamin W Deschner 1 2, Forrest W Williard 3, Justin A Drake 1, Ari Vanderwalde 4 5, Joanne Xiu 5, Bradley G Somer 4, Danny Yakoub 6, Miriam W Tsao 1 2, Evan S Glazer 1 2, Paxton V Dickson 1 2, David Shibata 1 2, Philip A Philip 7, Jimmy J Hwang 8, Anthony F Shields 7, John L Marshall 9, W Michael Korn 10, Heinz-Josef Lenz 11, Jeremiah L Deneve

Abstract

Background and Objectives

Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP).

Methods

CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB).

Results

One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts’ age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds.

Conclusions

Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

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