Molecular Profiling of Appendiceal Adenocarcinoma and Comparison with Right-sided and Left-sided Colorectal Cancer.
Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: We observed high mutation rates in appendiceal adenocarcinoma samples for KRAS (55%), TP53 (40%), GNAS (31%), SMAD4 (16%), and APC (10%). Appendiceal adenocarcinoma exhibited higher mutation rates in KRAS and GNAS, and lower mutation rates in TP53, APC, and PIK3CA (6%) than colorectal cancers. PMP exhibited much higher mutation rates in KRAS (74%) and GNAS (63%), and much lower mutation rates in TP53 (23%), APC (2%), and PIK3CA (2%) than NOS. Alterations associated with immune checkpoint inhibitor response (MSI-high, TMB-high, PD-L1 expression) showed similar frequency in appendiceal adenocarcinoma compared with L-CRC, but not R-CRC, and those of NOS were higher than other subtypes of appendiceal adenocarcinoma and L-CRC. CONCLUSIONS: Molecular profiling of appendiceal adenocarcinoma revealed different molecular characteristics than noted in R-CRC and L-CRC, and molecular heterogeneity among the histopathologic subtypes of appendiceal adenocarcinoma. Our findings may be critical to developing an individualized approach to appendiceal adenocarcinoma treatment.
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Authors | Ryuma Tokunaga, Joanne Xiu, Curtis Johnston, Richard M Goldberg, Philip A Philip, Andreas Seeber, Madiha Naseem, Jae Ho Lo, Hiroyuki Arai, Francesca Battaglin, Alberto Puccini, Martin D Berger, Shivani Soni, Wu Zhang, Jimmy J Hwang, Anthony F Shields, John L Marshall, Hideo Baba, W Michael Korn, Heinz-Josef Lenz |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 25
Issue 10
Pg. 3096-3103
(05 15 2019)
ISSN: 1557-3265 [Electronic] United States |
PMID | 30692096
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2019 American Association for Cancer Research. |
Chemical References |
- Biomarkers, Tumor
- Chromogranins
- KRAS protein, human
- GNAS protein, human
- GTP-Binding Protein alpha Subunits, Gs
- Proto-Oncogene Proteins p21(ras)
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Topics |
- Adenocarcinoma
(genetics, pathology)
- Adenocarcinoma, Mucinous
(genetics, pathology)
- Appendiceal Neoplasms
(genetics, pathology)
- Biomarkers, Tumor
(genetics)
- Chromogranins
(genetics)
- Colorectal Neoplasms
(genetics, pathology)
- Female
- GTP-Binding Protein alpha Subunits, Gs
(genetics)
- Gene Expression Profiling
- High-Throughput Nucleotide Sequencing
(methods)
- Humans
- Male
- Microsatellite Instability
- Mutation
- Proto-Oncogene Proteins p21(ras)
(genetics)
- Pseudomyxoma Peritonei
(genetics, pathology)
- Retrospective Studies
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