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15357163mct200318-sup-241873_2_supp_6526767_qf4th9.docx (13.62 kB)

Supplementary appendix from Molecular Characterization of Appendiceal Goblet Cell Carcinoid

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posted on 2023-04-03, 18:22 authored by Hiroyuki Arai, Yasmine Baca, Francesca Battaglin, Natsuko Kawanishi, Jingyuan Wang, Shivani Soni, Wu Zhang, Joshua Millstein, Curtis Johnston, Richard M. Goldberg, Philip A. Philip, Andreas Seeber, Joanne Xiu, Jimmy J. Hwang, Anthony F. Shields, John L. Marshall, W. Michael Korn, Heinz-Josef Lenz

The methods in assessing microsatellite instability (MSI) and mismatch repair (MMR) status

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ARTICLE ABSTRACT

Goblet cell carcinoid (GCC) is a distinct subtype of appendiceal neoplasm that exhibits unique clinical and pathologic features. We aimed to reveal the molecular profiles of GCC compared with other appendiceal tumors, such as adenocarcinomas and neuroendocrine tumors. A total of 495 appendiceal tumor samples (53 GCCs, 428 adenocarcinomas, and 14 neuroendocrine tumors) were tested with next-generation sequencing (NGS) on a 592-gene panel and IHC. Microsatellite instability (MSI)/mismatch repair (MMR) status was tested with a combination of NGS, IHC, and fragment analyses. Tumor mutational burden (TMB) was evaluated by NGS, and PD-L1 expression was tested by IHC (SP142). The most prevalent mutated genes within GCCs were TP53 (24.0%), ARID1A (15.4%), SMAD4 (9.4%), and KRAS (7.5%). Pathway-specific alterations were dominantly observed in cell cycle, MAPK, epigenetic, and TGFβ signaling pathways. GCCs as compared with adenocarcinomas exhibited significantly lower mutation rates in KRAS, GNAS, and APC, and significantly higher mutation rates in CDH1, CHEK2, CDC73, ERCC2, and FGFR2. GCCs as compared with neuroendocrine tumors showed significantly lower mutation rates in KRAS, APC, BRCA2, and FANCA. In GCCs, MSI high/MMR deficient, TMB high (≥17 mutations/Mb), and PD-L1 expression were seen in 0.0%, 0.0%, and 2.0% of tumors, respectively. No significant differences were observed in any immunotherapy-related markers examined when compared with adenocarcinomas and neuroendocrine tumors. In conclusion, GCCs had considerably distinct mutational profiles compared with appendiceal adenocarcinomas and neuroendocrine tumors. Understanding these molecular characteristics may be critical for the development of novel and more effective treatment strategies for GCC.

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