In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 539-539
Abstract:
Colorectal cancer (CRC) develops through a polyp-to-cancer progression sequence, in which normal colorectal epithelium transforms into an adenoma, which then progresses to cancer via the accumulation of progressive molecular changes, including both genetic and epigenetic alterations. Given that Colon epithelial cells can acquire pro-tumorigenic mutations that are insufficient to cause morphological change, genetic alternations in adjacent tumor tissues are primed to become neoplastic cells. It is known that individuals with a personal history of colon adenomas or cancer are at increased risk for metachronous colon neoplasms. To examine the genetic alternations involving in a polyp-to-cancer progression sequence, whole-transcriptome expression profiling of resected normal tissues (N1 and N3), adenoma (A1 and A2), and colorectal cancer (C1) obtained from individuals was performed. Differentially expressed genes among groups were identified using Subio platform. GATK and haplotypecaller was used to compare the somatic mutations among three different tissues. Tophat, Cufflink, Mev, R was used for determining the expression levels. Splicegrapher and Genomon-fusion was used for identifying the fusion genes. Ordinal regression analysis was performed to characterize site-dependent expression profiles. Gene interaction was examined using String (Open database). All statistical tests were two-sided, except where noted. Expression profile showed that highly expressed genes associated with inflammation were detected in adenoma. Our results indicated that highly expressed genes associated with inflammation were initially found in adenoma tissues and its levels were consistent in carcinoma tissues. Number of somatic mutation was extremely increased in carcinoma tissues when compared to adenoma tissues. The same mutations in KRAS, CDKN2A(p16) and TP53 that were observed in carcinoma tissues. They were also present in normal tissues and adenoma tissues. Disruption of TP53, CDKN2A, and KRAS were all seen as possible initial events in tumorigenesis; the sequence of mutations (the tumor development pathway) differed among lesions. Also, unique somatic mutations were found 17 genes which were not exist in normal tissues. Those somatic mutations were found in carcinoma tissues. The results of fusion gene analysis showed that 9 fusion genes were detected. Four fusion genes (FIIR-RBM2292, ST7-AS1-ST7, MMP11-IGLL5, EXOC4-LOC101928861) was detected in all of tissues. Five fusion genes were found in normal tissues and adenoma tissues. Unique fusion gene in carcinoma tissue was not detected. One explanation for this increased risk could be field cancerization, which is a phenomenon in which the histologically normal tissue in an organ is primed to undergo transformation. Our analysis of genetic alterations in a single patient appears to be promising markers for field cancerization. Citation Format: Chansu Lee, Sung Noh Hong, Sungjin Kim, Sunghoon Cho, Sohyun Youn, Kwang-Sung Ahn, Young-Ho Kim. Analysis of genetic alternations in multiple tissue specimens from each patient: Implications for field-effect colon cancerization. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 539.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-539
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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