104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA.
In subset analyses of individual pathologies, HER2-amplified status (hazard ratio [HR] 2.05, P=.02), BRAF V600+ mutational status (HR 0.33, P=.04), lung adenocarcinoma histology (HR 1.89, P=.04), and ALK rearrangement (HR 6.36, P<.01) were also associated with RN.
The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.
This implies limiting the number of tissue slides despite the existence of specific and sensitive biomarkers (ALK, ROS1, BRAFV600E, PD-L1) and the obligation to distinguish lung adenocarcinoma (TTF-1 positive) from squamous cell carcinoma (p40 positive).
In the last decade it became evident that many lung adenocarcinomas (ADC) harbor key genetic alterations such as KRAS, EGFR or BRAF mutations as well as rearrangements of ROS1 or ALK that drive these tumors.
Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis.
The present study applied the competitive allele-specific TaqMan polymerase chain reaction (CastPCR) technology to the molecular detection of EGFR (del2235-2249, del2236-2250, T790M, L858R) and BRAF (V600E, G469A, D594G) mutations in 144 treatment-naive patients with lung adenocarcinoma, and analyzed the association between the mutation rates and patients' clinicopathological features.
Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians.
Gene alterations are significant in lung tumorigenesis, with certain genes (Kristen rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], and B-Raf proto-oncogene, serine/threonine kinase (BRAF)) possessing alterations important in the prognosis and treatment of lung adenocarcinoma.
IHC using the VE1 clone and FLEX linker is a specific method for the detection BRAFV600E and may be an alternative to molecular biology for the detection of mutations in lung adenocarcinomas.
Activating BRAF(V600E) (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients.
Tumour-to-tumour metastasis from papillary thyroid carcinoma with BRAF mutation to lung adenocarcinoma with EGFR mutation: the utility of mutation-specific antibodies.