Genomic Landscape of Appendiceal Neoplasms

被引：76

作者：

Ang, Celina S-P ^{[1
]}

Shen, John Paul ^{[2
]}

Hardy-Abeloos, Camille J. ^{[1
]}

Huang, Justin K. ^{[2
]}

Ross, Jeffrey S. ^{[1
,3
]}

Miller, Vincent A. ^{[4
]}

Jacobs, Miriam T. ^{[2
]}

Chen, Ingrid L. ^{[2
]}

Xu, David ^{[2
]}

Ali, Siraj M. ^{[4
]}

Baumgartner, Joel ^{[2
]}

Lowy, Andrew ^{[2
]}

Fanta, Paul ^{[1
,2
]}

Ideker, Trey ^{[1
,2
]}

Millis, Sherri Z. ^{[4
]}

Harismendy, Olivier ^{[2
]}

机构：

[1] Mt Sinai Hosp, New York, NY 10029 USA

[2] Univ Calif San Diego, La Jolla, CA 92093 USA

[3] Albany Med Coll, Albany, NY 12208 USA

[4] Fdn Med, Cambridge, MA USA

来源：

JCO PRECISION ONCOLOGY | 2018年 / 2卷

关键词：

SYSTEMIC CHEMOTHERAPY; CLINICOPATHOLOGICAL ANALYSIS; PERITONEAL CARCINOMATOSIS; MUCINOUS CARCINOMATOSIS; PSEUDOMYXOMA PERITONEI; LOW-GRADE; CANCER; ADENOCARCINOMA; FEATURES; ORIGIN;

D O I：

10.1200/PO.17.00302

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Purpose Appendiceal neoplasms are heterogeneous and are often treated with chemotherapy similarly to colorectal cancer (CRC). Genomic profiling was performed on 703 appendiceal cancer specimens to compare the mutation profiles of appendiceal subtypes to CRC and other cancers, with the ultimate aim to identify potential biomarkers and novel therapeutic targets. Methods Tumor specimens were submitted to a Clinical Laboratory Improvement Amendments-certified laboratory (Foundation Medicine, Cambridge, MA) for hybrid-capture-based sequencing of 3,769 exons from 315 cancer-related genes and 47 introns of 28 genes commonly rearranged in cancer. Interactions between genotype, histologic subtype, treatment, and overall survival (OS) were analyzed in a clinically annotated subset of 76 cases. Results There were five major histopathologic subtypes: mucinous adenocarcinomas (46%), adenocarcinomas (30%), goblet cell carcinoids (12%), pseudomyxoma peritonei (7.7%), and signet ring cell carcinomas (5.2%). KRAS (35% to 81%) and GNAS (8% to 72%) were the most frequent alterations in epithelial cancers; APC and TP53 mutations were significantly less frequent in appendiceal cancers relative to CRC. Low-grade and high-grade tumors were enriched for GNAS and TP53 mutations, respectively (both chi(2) P < .001). GNAS and TP53 were mutually exclusive (Bonferroni corrected P < .001). Tumor grade and TP53 mutation status independently predicted OS. The mutation status of GNAS and TP53 strongly predicted OS (median, 37.1 months for TP53 mutant v 75.8 GNAS-TP53 wild type v 115.5 GNAS mutant; log-rank P = .0031) and performed as well as grade in risk stratifying patients. Conclusion Epithelial appendiceal cancers and goblet cell carcinoids show differences in KRAS and GNAS mutation frequencies and have mutation profiles distinct from CRC. This study highlights the benefit of performing molecular profiling on rare tumors to identify prognostic and predictive biomarkers and new therapeutic targets. (C) 2018 by American Society of Clinical Oncology

引用

页码：1 / 18

页数：18

共 35 条

[1]

Genome-wide mutational landscape of mucinous carcinomatosis peritonei of appendiceal origin [J].