Unique genetic and survival characteristics of invasive mucinous adenocarcinoma of the lung

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

49 Scopus Citations
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Author(s)

  • Hyo Sup Shim
  • [Unknown] Mari-Kenudson
  • Matthew Liebers
  • Yoon Jin Cha
  • Quan Hoang Ho
  • Maristela Onozato
  • Long Phi Le
  • Rebecca S. Heist
  • A. John Iafrate

Detail(s)

Original languageEnglish
Pages (from-to)1156-1162
Journal / PublicationJournal of Thoracic Oncology
Volume10
Issue number8
Publication statusPublished - 1 Aug 2015
Externally publishedYes

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 stagematched 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.

Research Area(s)

  • Adenocarcinoma, Gene fusion, Lung, Mucinous, Mutation, Targeted therapy.

Citation Format(s)

Unique genetic and survival characteristics of invasive mucinous adenocarcinoma of the lung. / Shim, Hyo Sup; Mari-Kenudson, [Unknown]; Zheng, Zongli; Liebers, Matthew; Cha, Yoon Jin; Ho, Quan Hoang; Onozato, Maristela; Le, Long Phi; Heist, Rebecca S.; John Iafrate, A.

In: Journal of Thoracic Oncology, Vol. 10, No. 8, 01.08.2015, p. 1156-1162.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review