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

 Hyo Sup Shim  ;  Mari-Kenudson  ;  Zongli Zheng  ;  Matthew Liebers  ;  Yoon Jin Cha  ;  Quan Hoang Ho  ;  Maristela Onozato  ;  Long Phi Le  ;  Rebecca S. Heist  ;  A. John Iafrate 
 JOURNAL OF THORACIC ONCOLOGY, Vol.10(8) : 1156-1162, 2015 
Journal Title
Issue Date
Adenocarcinoma, Mucinous/genetics* ; Adenocarcinoma, Mucinous/mortality ; Adenocarcinoma, Mucinous/pathology ; Adult ; Aged ; Aged, 80 and over ; Antigens, Differentiation, B-Lymphocyte/genetics ; Class I Phosphatidylinositol 3-Kinases ; DNA Mutational Analysis ; DNA, Neoplasm/analysis ; Disease-Free Survival ; Female ; Histocompatibility Antigens Class II/genetics ; Humans ; Lung Neoplasms/genetics* ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutation ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local/genetics* ; Neuregulin-1/genetics ; Oncogene Fusion ; Oncogene Proteins, Fusion/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins p21(ras)/genetics* ; Receptor, Epidermal Growth Factor/genetics* ; Receptor, ErbB-2/genetics ; Receptor, trkA/genetics ; Tropomyosin/genetics ; Tumor Suppressor Protein p53/genetics ; Vesicle-Associated Membrane Protein 2/genetics
Lung ; Adenocarcinoma ; Mucinous ; Mutation ; Gene fusion ; Targeted therapy
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.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Cha, Yoon Jin(차윤진) ORCID logo https://orcid.org/0000-0002-5967-4064
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