TY - JOUR
T1 - Liquid biopsy for patients with IBD-associated neoplasia
AU - Kinugasa, Hideaki
AU - Hiraoka, Sakiko
AU - Nouso, Kazuhiro
AU - Yamamoto, Shumpei
AU - Hirai, Mami
AU - Terasawa, Hiroyuki
AU - Yasutomi, Eriko
AU - Oka, Shohei
AU - Ohmori, Masayasu
AU - Yamasaki, Yasushi
AU - Inokuchi, Toshihiro
AU - Takahara, Masahiro
AU - Harada, Keita
AU - Tanaka, Takehiro
AU - Okada, Hiroyuki
N1 - Funding Information:
This study was supported by JSPS KAKENHI (19 k17433). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12
Y1 - 2020/12
N2 - Background: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.
AB - Background: It is often difficult to diagnose inflammatory bowel disease (IBD)-associated neoplasia endoscopically due to background inflammation. In addition, due to the absence of sensitive tumor biomarkers, countermeasures against IBD-associated neoplasia are crucial. The purpose of this study is to develop a new diagnostic method through the application of liquid biopsy. Methods: Ten patients with IBD-associated cancers and high-grade dysplasia (HGD) with preserved tumor tissue and blood were included. Tumor and non-tumor tissues were analyzed for 48 cancer-related genes using next-generation sequencing. Simultaneously, circulating tumor DNA (ctDNA) was analyzed for mutations in the target genes using digital PCR. Results: Out of 10 patients, seven had IBD-related cancer and three had IBD-related HGD. Two patients had carcinoma in situ; moreover, three had stageII and two had stage III. To avoid false positives, the mutation rate cutoff was set at 5% based on the control results; seven of 10 (70%) tumor tissue samples were mutation-positive. Mutation frequencies for each gene were as follows: TP53 (20.9%; R136H), TP53 (25.0%; C110W), TP53 (8.5%; H140Q), TP53 (31.1%; R150W), TP53 (12.8%; R141H), KRAS (40.0%; G12V), and PIK3CA (34.1%; R 88Q). The same mutations were detected in the blood of these seven patients. However, no mutations were detected in the blood of the remaining three patients with no tumor tissue mutations. The concordance rate between tumor tissue DNA and blood ctDNA was 100%. Conclusion: Blood liquid biopsy has the potential to be a new method for non-invasive diagnosis of IBD-associated neoplasia.
KW - IBD-associated cancer
KW - IBD-associated neoplasia
KW - Liquid biopsy
KW - ctDNA
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U2 - 10.1186/s12885-020-07699-z
DO - 10.1186/s12885-020-07699-z
M3 - Article
C2 - 33272240
AN - SCOPUS:85097005200
SN - 1471-2407
VL - 20
JO - BMC cancer
JF - BMC cancer
IS - 1
M1 - 1188
ER -
