ABSTRACT
Purpose@#Loss-of-function mutations in the adenomatous polyposis coli (APC) gene are common in metastatic colorectal cancer (mCRC). However, the characteristic of APC specific mutations in mCRC is poorly understood. Here, we explored the clinical and molecular characteristics of N-terminal and C-terminal side APC mutations in Chinese patients with mCRC. @*Materials and Methods@#Hybrid capture-based next-generation sequencing was performed on tumor tissues from 275 mCRC pati-ents to detect mutations in 639 tumor-associated genes. The prognostic value and gene-pathway difference between APC specific mutations in mCRC patients were analyzed. @*Results@#APC mutations were highly clustered, accounting for 73% of all mCRC patients, and most of them were truncating mutations. The tumor mutation burden of the N-terminal side APC mutations group (n=76) was significantly lower than that of the C-terminal side group (n=123) (p < 0.001), further confirmed by the public database. Survival analysis showed that mCRC patients with N-terminus side APC mutations had longer overall survival than C-terminus side. Tumor gene pathway analysis showed that gene mutations in the RTK/RAS, Wnt and transforming growth factor β signaling pathways of the C-terminal group were significantly higher than those of the N-terminal group (p < 0.05). Additionally, KRAS, AMER1, TGFBR2, and ARID1A driver mutations were more common in patients with C-terminal side APC mutations. @*Conclusion@#APC specific mutations have potential function as mCRC prognostic biomarkers. There are obvious differences in the gene mutation patterns between the C-terminus and N-terminus APC mutations group, which may have certain guiding significance for the subsequent precise treatment of mCRC.
ABSTRACT
Objective@#To evaluate the clinical application of bronchial washing fluid (BWF) in the detection of epidermal growth factor receptor (EGFR) gene mutation in lung cancer patients during diagnostic bronchoscopic procedure.@*Methods@#Patients with suspected lung cancer lesions but failed to be identified as malignancy by rapid on-site cytologic evaluation (ROSE) were enrolled. Performed blocker PCR for EGFR mutation detection using the supernatant and cell pellet of BWF samples and compared the detective results to the EGFR mutation status detected using histologic tumor samples.@*Results@#A total of 85 BWF and paired histological samples were collected at Fudan University Affiliated Zhongshan Hospital from October 2016 to June 2017. There were 46 male and 39 female, with a mean age of 61 years (range 30-87 years). Thirty-one patients had benign diseases and 54 patients had primary lung cancer. Among these 54 lung cancer patients, the diagnoses were made basing on bronchoscopic biopsy samples in 31 patients. The detection rate of EGFR gene mutation in BWF samples was 100.0% concordant with that using histological samples.Another 23 cases whose bronchoscopic biopsy failed to establish malignant diagnoses were further identified by other sampling methods including surgical resection, lung biopsy, etc. A total of 15 patients were identified as EGFR mutated type by pathologic detection or clinically effect assessment, and BWF could detect 11 of them, accounting for 11/15 of all cases. Overall, BWF had achieved an overall accuracy of 95.3% (81/85) comparing to paired tumor histologic samples.@*Conclusions@#BWF is an effective complementary specimen to bronchoscopic biopsy samples in EGFR gene mutation detection in patients with suspected lung cancer lesion and negative biopsy results evaluated by ROSE during bronchoscopy.