TY - JOUR
T1 - Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis
AU - Fleming, Andrew M.
AU - Deschner, Benjamin W.
AU - Williard, Forrest W.
AU - Drake, Justin A.
AU - Vanderwalde, Ari
AU - Xiu, Joanne
AU - Somer, Bradley G.
AU - Yakoub, Danny
AU - Tsao, Miriam W.
AU - Glazer, Evan S.
AU - Dickson, Paxton V.
AU - Shibata, David
AU - Philip, Philip A.
AU - Hwang, Jimmy J.
AU - Shields, Anthony F.
AU - Marshall, John L.
AU - Korn, W. Michael
AU - Lenz, Heinz Josef
AU - Deneve, Jeremiah L.
N1 - Publisher Copyright:
© 2023 Wiley Periodicals LLC.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - appendiceal neoplasms
KW - colorectal neoplasms
KW - neoplasm metastasis
KW - peritoneal neoplasms
KW - peritoneum
UR - https://www.scopus.com/pages/publications/85146232070
UR - https://www.scopus.com/pages/publications/85146232070#tab=citedBy
U2 - 10.1002/jso.27198
DO - 10.1002/jso.27198
M3 - Article
C2 - 36629137
AN - SCOPUS:85146232070
SN - 0022-4790
VL - 127
SP - 815
EP - 822
JO - Journal of Surgical Oncology
JF - Journal of Surgical Oncology
IS - 5
ER -
