Identification and validation of PROM1 and CRTC2 mutations in lung cancer patients

Abstract

Background: Genetic alterations could be responsible lung cancer, the leading cause of worldwide cancer death.

Methods: This study investigated gene mutations in a Han Chinese family of lung cancer using the whole genome exome sequencing and subsequent Sanger sequencing validation and then confirmed alteration of prominin 1(PROM1) and cyclic AMP-response element binding protein-regulated transcription co-activator2 (CRTC2) in blood samples of 343 sporadic lung cancer patients vs. 280 healthy controls as well as in 200 pairs of lung cancer and the corresponding normal tissues using PCR-restriction fragment length polymorphism and directed DNA sequencing of PCR products.

Results: The data showed PROM1 (p. S281R) and CRTC2 (p. R379C) mutations, in 5 and 2 cases of these 343 sporadic lung cancer patients, respectively. Notably, these mutations were absent in the healthy controls. Furthermore, in the 200 lung cancer and the matched normal tissues, PROM1 mutation occurred in 3 patients (i.e., one squamous cell carcinoma and two adenocarcinomas) with a mutation frequency of 1.5%, while CRTC2 mutation occurred in 5 patients (two squamous cell carcinomas and three adenocarcinomas) with a mutation frequency of 2.5%.

Conclusions: The data from the current study demonstrated novel PROM1 and CRTC2 mutations, which could promote lung cancer development.

Figure 1

Somatic gene mutations in III-1 patient. A, PROM1mutation. B, CRTC2 mutation. Tumor genomic DNA of the affected family, genomic DNA of blood sample from lung cancer patient, genomic DNA from lung cancer and the matched normal tissues.

Figure 2

Pedigree of this lung cancer family. Hepatocarcinoma occurred in I-2, II-3, and III-2; lung cancer in II-2, II-4, and III-1; and gastric cancer in II-5.