Introduction: Although KRAS mutations in NSCLC have been considered mutually exclusive driver mutations for a long time, there is now growing evidence that KRASmutated NSCLC represents a genetically heterogeneous subgroup. We sought to determine genetic heterogeneity with respect to cancer-related co-mutations and their correlation with different KRAS mutation subtypes.

and mutations are associated with impaired prognosis in a variety of cancers and with squamous cell carcinoma formation in non-small cell lung cancer (NSCLC). However, little is known about frequency, histology dependence, molecular and clinical presentation as well as response to systemic treatment in NSCLC. Tumor tissue of 1,391 patients with NSCLC was analyzed using next-generation sequencing (NGS). Clinical and pathologic characteristics, survival, and treatment outcome of patients with or mutations were assessed. mutations occurred with a frequency of 11.3% ( = 157) and mutations with a frequency of 3.5% ( = 49) in NSCLC patients. In the vast majority of patients, both mutations did not occur simultaneously. mutations were found mainly in adenocarcinoma (AD; 72%), while mutations were more common in squamous cell carcinoma (LSCC; 59%). mutations were spread over the whole protein, whereas mutations were clustered in specific hotspot regions. In over 80% of the patients both mutations co-occurred with other cancer-related mutations, among them also targetable aberrations like activating mutations or amplification. Both patient groups showed different patterns of metastases, stage distribution and performance state. No patient with mutation had a response on systemic treatment in first-, second-, or third-line setting. Of-mutated patients, none responded to second- or third-line therapy.- and -mutated NSCLC patients represent a highly heterogeneous patient cohort. Both are associated with different histologies and usually are found together with other cancer-related, partly targetable, genetic aberrations. In addition, both markers seem to be predictive for chemotherapy resistance..

No abstract

No abstract

No abstract

No abstract

<p>Main characteristics of the control group.</p>

No abstract