Moreover, the non-adenocarcinoma (SCLC) component might arise from the adenocarcinoma (NSCLC) component through a mechanism that involves the activation of the ASCL1 and PI3K/AKT1 signaling pathways.
In squamous cell carcinomas more often multiple mutations per sample (p=0.040), and more PIK3CA (p=0.039) and CTNNB1 (p=0.038) mutations were detected compared to adenocarcinomas.
Here we report measurements of PIK3CAH1047R mutant fraction (MF) in normal colonic mucosa, normal lung, colonic adenomas, colonic adenocarcinomas, and lung adenocarcinomas.
The activated pathway in lung ADC and SCC mainly focuses on MAPK and PI3K with different key genes of each, respectively, and the activated pathway of SCLC mainly focuses on JAK-STAT pathway.
Patient harboring a novel PIK3CA point mutation after acquired resistance to crizotinib in an adenocarcinoma with ROS1 rearrangement: A case report and literature review.
GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043).
Of 24 patients with actionable mutations, five were given genotype-matched drugs corresponding to actionable mutations: everolimus to PIK3CA mutation in parotid carcinosarcoma (partial response) and tracheal squamous cell carcinoma (stable disease; 21% reduction), sorafenib to PDGFRA mutation in auditory canal adenocarcinoma (partial response), sorafenib to BRAF mutation in microcytic adnexal carcinoma (progressive disease), and afatinib to ERBB2 mutation in esophageal adenocarcinoma (progressive disease).
Synchronous lung cancers from 60 patients (42 with adenocarcinoma and 18 with squamous cell carcinoma), clinically considered to represent intrapulmonary metastases, were histologically subtyped according to the 2015 World Health Organization classification of lung tumors and subjected to genotypic analysis (KRAS, EGFR, BRAF, PIK3CA, ALK, MET and ROS1 in adenocarcinoma and PIK3CA and p16 in squamous cell carcinoma).
PIK3CA mutations occurred more frequently in SCC than AC (25% vs. 11%, P=0.025), whereas KRAS mutations occurred more frequently in AC than SCC (24% vs. 3%, P<0.001) and ASC (24% vs. 3%, P<0.001).
We hypothesize that calmodulin recruits and helps activate PI3Kα at the membrane, and that this is the likely reason for Ca(2+)/calmodulin dependence in adenocarcinomas.
CHFR expression, analyzed by RNA-seq, was classified as high vs. low based on the median CHFR expression level and correlated with the presence or absence of lung cancer specific mutations (EGFR, KRAS, ALK, MET, ERBB2, TP53, STK11, ROS1, RET, NF1, Pik3CA for adenocarcinomas and FGFR1, FGFR2, FGFR3, TP53, STK11, EGFR for squamous cell carcinomas).
PIK3CA-mutated NSCLC represents a clinically and genetically heterogeneous subgroup in adenocarcinomas as well as in squamous cell carcinomas with a higher prevalence of these mutations in sqamous cell carcinoma.
When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA.
Single nucleotide substitutions in TP53 and PIK3CA genes were detected in 36% and 11% of adenocarcinoma, in 16% and in 5% of squamous cell carcinoma, and in 13% and none of CIN 3, respectively.
Patients with adenocarcinoma had fewer PIK3CA mutations (14%), and survived longer (median, 14.2 months) than those with squamous cell carcinoma (48% and 7.2 months; p = 0.016, and 0.001, respectively).
In highly differentiated adenocarcinomas the ErbB2/ErbB3 complex is activated, which is followed by phosphatidylinositol 3-kinase (PI3K) activation. p38 MAP kinase is activated downstream of PI3K and adherens junctions are disrupted via Rac1 activation.
The most prevalent biomarkers in pulmonary adenocarcinoma were KRAS mutations (29%), loss of PTEN expression (18%), EGFR mutations (9%), HER2 amplification (5%) and BRAF mutations (3%), while the prevalence of ALK translocations and PIK3CA mutations was extremely low.