TY - JOUR
T1 - Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel
AU - Scarpa, Aldo
AU - Sikora, Katarzyna
AU - Fassan, Matteo
AU - Rachiglio, Anna Maria
AU - Cappellesso, Rocco
AU - Antonello, Davide
AU - Amato, Eliana
AU - Mafficini, Andrea
AU - Lambiase, Matilde
AU - Esposito, Claudia
AU - Bria, Emilio
AU - Simonato, Francesca
AU - Scardoni, Maria
AU - Turri, Giona
AU - Chilosi, Marco
AU - Tortora, Giampaolo
AU - Fassina, Ambrogio
AU - Normanno, Nicola
PY - 2013/11/13
Y1 - 2013/11/13
N2 - Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy.
AB - Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy.
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U2 - 10.1371/journal.pone.0080478
DO - 10.1371/journal.pone.0080478
M3 - Article
C2 - 24236184
AN - SCOPUS:84893411121
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 11
M1 - e80478
ER -