Abstract
KRAS is the most commonly mutated oncogene in human cancers. Targeted therapy and immunotherapy for this gene have made remarkable progress in recent years. However, comprehensive molecular landscape analysis of KRAS in rare tumors is lacking. Retrospective analysis was performed on clinical samples from patients with rare tumors collected between September 2015 and September 2021, using hybrid-capture-based next-generation sequencing for genomic profiling and immunohistochemistry assay for PD-L1. Of the 3,453 patients included in analysis, KRAS mutations were identified in 8.7% patients in overall; mutation rate and mutation subtypes varied widely across tumor systems and subtypes. KRAS mutations included 21 missense mutations, of which G12D (29.2%), G12V (24.6%), and G13D (10.8%) were most common. Interestingly, KRAS G12C was observed in 0.6% patients overall, and in 5.7% of sarcomatoid carcinoma of the lung and 5.4% of clear cell ovarian cancer tumors, but none in small-bowel cancer tumors. 31.8% KRAS mutations and 36.4% KRAS G12C mutations co-occurred with other targetable alterations. No significant correlation was observed between TMB-H, MSI-H, PD-L1 status, and KRAS mutation status, which may be related to the high proportion of G12D. This study is the first KRAS mutation landscape study in rare tumors of large sample size in China and worldwide. Our results suggest that targeted therapy and immunotherapy are both feasible, albeit complex, in these patients. This information may have significant impact on the operation of clinical trials for rare tumor patients with KRAS mutations in China.
Highlights
Rare cancers are roughly defined as cancers with fewer than 15 new diagnoses in 100,000 people a year, but there is no universally adopted definition (Abbas-Aghababazadeh et al, 2020)
By analysing the correlation between Kirsten rat sarcoma (KRAS) and immunotherapeutic molecular markers, we found that KRAS mutation was not related to tumour mutational burden (TMB)-H (p = 0.45), microsatellite instability (MSI)-H (p = 0.41) or programmed cell death ligand-1 (PD-L1) (p = 0.35) (Figure 3)
In addition to small bowel cancer and cholangiocarcinoma, we found a high prevalence of KRAS mutations in sarcomatoid carcinoma of the lung (SARCL), OOCV, cancer of unknown primary (CUP), and Neuroendocrine tumors (NETs)
Summary
Rare cancers are roughly defined as cancers with fewer than 15 new diagnoses in 100,000 people a year, but there is no universally adopted definition (Abbas-Aghababazadeh et al, 2020). Sarcomatoid carcinoma of the lung (SARCL) is rare tumor, with
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
