Satu Mäki-Nevala1, Virinder Kaur Sarhadi2, Mikko Rönty3, Eeva Kettunen4, Kirsti Husgafvel-Pursiainen5, Henrik Wolff6, Aija Knuuttila7, Sakari Knuutila8. 1. University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: satu.maki-nevala@helsinki.fi. 2. University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: virinder.sarhadi@helsinki.fi. 3. Helsinki University Central Hospital, HUSLAB, Department of Pathology, P.O. Box 400, 00029 Helsinki, Finland. Electronic address: mikko.ronty@helsinki.fi. 4. Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: eeva.kettunen@ttl.fi. 5. Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: kirsti.husgafvel-pursiainen@ttl.fi. 6. Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: henrik.wolff@ttl.fi. 7. University of Helsinki and Helsinki University Hospital, Heart and Lung Center, Department of Pulmonary Medicine, P.O. Box 340, 00029 Helsinki, Finland. Electronic address: aija.knuuttila@hus.fi. 8. University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: sakari.knuutila@helsinki.fi.
Abstract
OBJECTIVES: Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. MATERIALS AND METHODS: Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). RESULTS: Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. CONCLUSION: Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations.
OBJECTIVES:Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. MATERIALS AND METHODS: Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). RESULTS: Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. CONCLUSION: Finnish NSCLCpatients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations.
Authors: Anand Khadse; Vilde D Haakensen; Laxmi Silwal-Pandit; Julian Hamfjord; Patrick Micke; Johan Botling; Odd Terje Brustugun; Ole Christian Lingjærde; Åslaug Helland; Elin H Kure Journal: Front Oncol Date: 2022-04-29 Impact factor: 5.738
Authors: Javier Mariscal; Marta Alonso-Nocelo; Laura Muinelo-Romay; Jorge Barbazan; Maria Vieito; Alicia Abalo; Antonio Gomez-Tato; Casares de Cal Maria de Los Angeles; Tomas Garcia-Caballero; Carmela Rodriguez; Elena Brozos; Francisco Baron; Rafael Lopez-Lopez; Miguel Abal Journal: Sci Rep Date: 2016-11-30 Impact factor: 4.379
Authors: Kajsa Ericson Lindquist; Anna Karlsson; Per Levéen; Hans Brunnström; Christel Reuterswärd; Karolina Holm; Mats Jönsson; Karin Annersten; Frida Rosengren; Karin Jirström; Jaroslaw Kosieradzki; Lars Ek; Åke Borg; Maria Planck; Göran Jönsson; Johan Staaf Journal: Oncotarget Date: 2017-05-23