Pulmonary Adenocarcinoma In Situ and Minimally Invasive Adenocarcinomas in European Patients Have Less KRAS and More EGFR Mutations Compared to Advanced Adenocarcinomas.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Adenocarcinoma in Situ*/genetics ; Adenocarcinoma in Situ*/pathology ; Adenocarcinoma of Lung*/genetics ; Adenocarcinoma*/pathology ; Lung Neoplasms*/metabolism; Humans ; Proto-Oncogene Proteins p21(ras)/genetics ; Mutation ; ErbB Receptors/metabolism

Pulmonary adenocarcinoma (ADC) is a very diverse disease, both genetically and histologically, which displays extensive intratumor heterogeneity with numerous acquired mutations. ADC is the most common type of lung cancer and is believed to arise from adenocarcinoma in situ (AIS) which then progresses to minimally invasive adenocarcinoma (MIA). In patients of European ethnicity, we analyzed genetic mutations in AIS ( n = 10) and MIA ( n = 18) and compared the number of genetic mutations with advanced ADC ( n = 2419). Using next-generation sequencing, the number of different mutations detected in both AIS (87.5%) and MIA (94.5%) were higher ( p < 0.001) than in advanced ADC (53.7%). In contrast to the high number of mutations in Kirsten rat sarcoma virus gene ( KRAS ) in advanced ADC (34.6%), there was only one case of AIS with KRAS G12C mutation (3.5%; p < 0.001) and no cases of MIA with KRAS mutation ( p < 0.001). In contrast to the modest prevalence of epidermal growth factor receptor ( EGFR ) mutations in advanced ADC (15.0%), the fraction of EGFR mutant cases was higher in both in AIS (22.2%) and MIA (59.5%; p < 0.001). The EGFR exon 19 deletion mutation was more common in both MIA (50%; n = 6/12) and ADC (41%; n = 149/363), whereas p.L858R was more prevalent in AIS (75%; n = 3/4). In contrast to pulmonary advanced ADC, KRAS driver mutations are less common, whereas mutations in EGFR are more common, in detectable AIS and MIA.

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17 0171 Strategic Fund from the Institute of Biomedicine, University of Gothenburg, the Swedish Cancer Foundation; ALFGBG-495961 ALF fund from the Sahlgrenska Academy Hospital in the Västra Götalandsre-gionen; FB20-87 Assar Gabrielsson's Foundation; GU 2020/751 Adlerbertska Forskningsstiftelsen

Keywords: EGFR; KRAS; biomarker; lung adenocarcinoma; mutation

EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
EC 2.7.10.1 (ErbB Receptors)
0 (KRAS protein, human)
EC 2.7.10.1 (EGFR protein, human)

Date Created: 20240313 Date Completed: 20240314 Latest Revision: 20240315

20240315

PMC10932068

10.3390/ijms25052959

38474205