Acquired somatic TP53 or PIK3CA mutations are potential predictors of when polyps evolve into colorectal cancer

// Pi-Yueh Chang 1, 2 , Jinn-Shiun Chen 3 , Shih-Cheng Chang 1, 2 , Mei-Chia Wang 1, 2 , Nai-Chung Chang 1 , Ying-Hao Wen 1 , Wen-Sy Tsai 3 , Wei-Hsiu Liu 1 , Hsiu-Ling Liu 1 and Jang-Jih Lu 1, 2 1 Department of Laboratory Medicine, Chang Gung Memorial Hospital at LinKou, Taoyuan, Taiwan 2 Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan 3 Department of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan Correspondence to: Jang-Jih Lu, email: janglu45@gmail.com , jjlpcp@adm.cgmh.org.tw Keywords: next-generation sequencing, polyps, colorectal cancer, ampliseq cancer hotspot panel, synchronous neoplasm Received: May 23, 2017      Accepted: August 07, 2017      Published: August 21, 2017 ABSTRACT Colorectal cancer (CRC) develops from accumulated mutations. However, which gene determines the malignant transformation from adenoma to carcinoma is still uncertain. Fifty-three formalin fixed paraffin-embedded polyps that had pathological findings from patients with hyperplasia, adenomatous, and tubular adenoma < 1 cm (non-neoplasia polyps, NNP, n = 27) or tubular adenoma ≥ 1 cm, tubulovillous and villous adenoma (neoplastic polyps, NP, n = 26) were recruited. Six paired synchronous polyps and cancer tissues and 50 independent fresh CRC tumors were also collected. All tissues were analyzed for their mutation genomes using next generation sequencing with a 50-gene panel. There were 40 types of somatic variants found in 7 genes, APC (43%), KRAS (28%), TP53 (11%), FBXW7 (8%), GNAS (4%), SMAD4 (2%), and BRAF (2%), and they were detected in 32 (60%) polyps. If combined with the mutation spectrum found in CRC tissues, a significant increase in the mutation rate in TP53 and PIK3CA from NNP, NP, early and late stage carcinoma (7%, 15%, 33.3% and 65% for TP53, p < 0.001; 0%, 0%, 23.3% and 25% for PIK3CA , p = 0.002) were noticed. Furthermore, distinct molecular features can be found in five pairs of synchronous polyps and tumors. However, TP53 or PIK3CA mutations can be found in tumor tissues but not in polyps. By systematically investigating the genome from polyps to tumor tissues, we demonstrated that acquired TP53 or PIK3CA somatic mutations are potential predictors for malignancy development. These results may aid in the identification of high risk individuals with tissues harboring mutations in these two genes.