TY - JOUR
T1 - Deep sequencing analysis reveals that KRAS mutation is a marker of poor prognosis in patients with pulmonary sarcomatoid carcinoma
AU - Lococo, Filippo
AU - Gandolfi, Greta
AU - Rossi, Giulio
AU - Pinto, Carmine
AU - Rapicetta, Cristian
AU - Cavazza, Alberto
AU - Cesario, Alfredo
AU - Galeone, Carla
AU - Paci, Massimiliano
AU - Ciarrocchi, Alessia
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - KRAS
KW - Next-generation sequencing
KW - Oncology
KW - Pulmonary and Respiratory Medicine
KW - Pulmonary carcinosarcoma
KW - Pulmonary sarcomatoid tumor
KW - Survival probability
KW - KRAS
KW - Next-generation sequencing
KW - Oncology
KW - Pulmonary and Respiratory Medicine
KW - Pulmonary carcinosarcoma
KW - Pulmonary sarcomatoid tumor
KW - Survival probability
UR - http://hdl.handle.net/10807/99991
UR - http://journals.lww.com/jto
U2 - 10.1016/j.jtho.2016.04.020
DO - 10.1016/j.jtho.2016.04.020
M3 - Article
SN - 1556-0864
VL - 11
SP - 1282
EP - 1292
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
ER -