Deep sequencing analysis reveals that KRAS mutation is a marker of poor prognosis in patients with pulmonary sarcomatoid carcinoma

Filippo Lococo*, Greta Gandolfi, Giulio Rossi, Carmine Pinto, Cristian Rapicetta, Alberto Cavazza, Alfredo Cesario, Carla Galeone, Massimiliano Paci, Alessia Ciarrocchi

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivista

35 Citazioni (Scopus)


Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subset of non-small cell lung cancer with limited treatment options. The molecular characterization of PSC has been strongly hampered by the relative rarity of these tumors. However, understanding the molecular and genetic bases of PSCs is critical to pave the way to new treatment options. In this work, we aimed to explore the complexity of the genetic asset of PSC and investigate its prognostic impact on survival in a large cohort of patients with PSC. Methods: Next-generation sequencing analysis of a panel of 26 genes with potential clinical relevance was performed on surgical specimens of 49 PSCs. The prognostic impact of genetic profiles on patient survival and the association between the genetic alterations and clinicopathological features were tested. Results: Fifty-five somatic mutations were detected in 13 genes. Thirty-nine PSCs (80%) showed at least one mutation. Survival probability decreased in patients with mutated PSC compared with in those with PSC without mutations (p = 0.02). In particular, mutations in Kirsten rat sarcoma viral oncogene homolog gene (KRAS), alone or in combination with tumor protein p53 gene (TP53) mutations, were associated with decreased survival probability and with the occurrence of local metastases at recurrence. Finally, comparison of our results with data in The Cancer Genome Atlas showed that PSCs have a mutational profile similar to that of smokers' lung adenocarcinoma. Conclusions: Overall, our analysis provides further information on the mutational profiles of PSCs and demonstrates for the first time a role of KRAS mutations in driving the aggressiveness of this type of cancer.
Lingua originaleEnglish
pagine (da-a)1282-1292
Numero di pagine11
RivistaJournal of Thoracic Oncology
Stato di pubblicazionePubblicato - 2016


  • KRAS
  • Next-generation sequencing
  • Oncology
  • Pulmonary and Respiratory Medicine
  • Pulmonary carcinosarcoma
  • Pulmonary sarcomatoid tumor
  • Survival probability


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