RAS Mutations Coexist with PIK3CA and MET Mutations in Lacrimal Gland Epithelial Neoplasms

Purpose: Oncogenic mutations for PIK3CA, RAS (KRAS, NRAS), BRAF and MET have been identified in various malignancies, and activate the PI3K/ AKT/mTOR and RAS/RAF/MEK pathways respectively. Both pathways are critical drivers of tumorigenesis.

Methods: Tumor tissue from 24 patients with lacrimal gland epithelial neoplasms (3 benign pleomorphic adenomas and 21 malignant: 16 adenoid cystic carcinomas, 2 low grade carcinoma-ex pleomorphic adenomas, 2 high grade carcinoma-ex pleomorphic adenoma, one squamous carcinoma treated at M. D. Anderson Cancer Center were analyzed for PIK3CA, RAS (KRAS, NRAS), BRAF and MET using polymerase chain-reaction based DNA sequencing.

Results: KRAS mutations were found in 11 (46%) of 24 patients tested; NRAS in 2 (8%) of 24 patients tested; MET in 3 (13%) of 24 patients tested; PIK3CA in 1 (4%) of 24 patients tested; BRAF in 0 of 24 patients tested.

Half of oncogenic mutations were found in adenoid cystic carcinoma (9/16, 56%). KRAS mutations were most frequent in adenoid cystic carcinoma (6/11, 55%), as well as MET mutations (⅔, 67%), NRAS mutations (½, 50%) and none for PIK3CA or BRAF.

In one benign mixed tumor KRAS mutations coexisted with NRAS and PIK3CA; in another benign mixed tumor both KRAS and NRAS mutations were found. One high grade carcinoma was found to have concurrent KRAS and MET mutations.

Conclusions: RAS (KRAS, NRAS), PIK3CA and MET mutations are frequent in diverse epithelial neoplasms of lacrimal gland with the highest proportion of mutations found in adenoid cystic carcinoma. PIK3CA and MET mutations can coexist with RAS mutations.