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Unique Genetic and Survival Characteristics of Invasive Mucinous Adenocarcinoma of the Lung

Authors
 Hyo Sup Shim ; Mari-Kenudson ; A. John Iafrate ; Rebecca S. Heist ; Long Phi Le ; Maristela Onozato ; Quan Hoang Ho ; Yoon Jin Cha ; Matthew Liebers ; Zongli Zheng 
Citation
 Journal of Thoracic Oncology, Vol.10(8) : 1156~1162, 2015 
Journal Title
 Journal of Thoracic Oncology 
ISSN
 1556-0864 
Issue Date
2015
Abstract
INTRODUCTION: Invasive mucinous adenocarcinoma is a unique histologic subtype of lung cancer, and our knowledge of its genetic and clinical characteristics is rapidly evolving. Here, we present next- generation sequencing analysis of nucleotide variant and fusion events along with clinical follow-up in a series of lung mucinous adenocarcinoma. METHODS: We collected 72 mucinous adenocarcinomas from the United States and Korea. All had been previously assessed for KRAS and EGFR mutations. For KRAS wild-type cases (n = 30), we performed deep targeted next-generation sequencing for gene fusions and nucleotide variants and correlated survival and other clinical features. RESULTS: As expected, KRAS mutations were the most common alteration found (63% of cases); however, the distribution of nucleotide position alterations was more similar to that observed in gastrointestinal tumors than other lung tumors. Within the KRAS-negative cases, we found numerous potentially targetable gene fusions and mutations, including CD74-NRG1, VAMP2-NRG1, TRIM4-BRAF, TPM3-NTRK1, and EML4-ALK gene fusions and ERBB2, BRAF, and PIK3CA mutations. Unexpectedly, we found only two cases with TP53 mutation, which is much lower than observed in lung adenocarcinomas in general. The overall mutation burden was low in histologically confirmed mucinous adenocarcinomas from the public The Cancer Genome Atlas exome data set, regardless of smoking history, suggesting a link between TP53 status and mutation burden in mucinous tumors. There was no significant difference for recurrence-free survival between stage-matched mucinous and nonmucinous adenocarcinomas. It was notable that all recurrence sites were in the lungs for completely resected cases. CONCLUSIONS: Our data suggest that mucinous adenocarcinoma is typified by (1) frequent KRAS mutations and a growing list of gene fusions, but rare TP53 mutations, (2) a low mutation burden overall, and (3) a recurrence-free survival similar to stage-matched nonmucinous tumors, with recurrences limited to the lungs.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/141036
DOI
10.1097/JTO.0000000000000579
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
Yonsei Authors
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Link
 http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=01243894-201508000-00007&LSLINK=80&D=ovft
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