Abstract
Clinicopathological characteristics and survival in metastatic colorectal cancer with short-form APC mutations.
Author
person
Hiroki Osumi
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
info_outline
Hiroki Osumi, Akira Ooki, Ippei Fukada, Koichiro Yoshino, Mikako Tamba, Shohei Udagawa, Shota Fukuoka, Takeru Wakatsuki, Mariko Ogura, Daisuke Takahari, Keisho Chin, Hideaki Bando, Takayuki Yoshino, Naomi Hayashi, Shunji Takahashi, Kensei Yamaguchi, Hiroyuki Seimiya, Eiji Shinozaki, Yoshiaki Nakamura
Full text
Authors
person
Hiroki Osumi
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
info_outline
Hiroki Osumi, Akira Ooki, Ippei Fukada, Koichiro Yoshino, Mikako Tamba, Shohei Udagawa, Shota Fukuoka, Takeru Wakatsuki, Mariko Ogura, Daisuke Takahari, Keisho Chin, Hideaki Bando, Takayuki Yoshino, Naomi Hayashi, Shunji Takahashi, Kensei Yamaguchi, Hiroyuki Seimiya, Eiji Shinozaki, Yoshiaki Nakamura
Organizations
Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Translational Research Support Office, Division of Drug and Diagnostic Development Promotion, Department for the Promotion of Drug and Diagnostic Development, National Cancer Center Hospital East, Kashiwa, Japan, National Cancer Center Hospital East, Kashiwa, Japan, Genomic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan, Department of Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan, Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan, Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
Abstract Disclosures
Research Funding
No funding sources reported
Background:
Wnt/β-catenin signaling is activated by loss-of-function mutations in the
adenomatous polyposis coli
(
APC
) gene and plays a key role in tumorigenesis in colorectal cancer (CRC). Tankyrase inhibitors, which cause degradation of β-catenin, are expected to have a promising therapeutic effect for CRC, and the short-form
APC
mutations predict the sensitivity of CRC cells to tankyrase inhibitors (Tanaka et al.
Mol Cancer Ther
2017; Chen et al.
Br J Cancer
, in press).However, clinicopathological characteristics and survival in metastatic CRC (mCRC) with short-form
APC
mutations remain unclear.
Methods:
Patients with mCRC who were treated with chemotherapy between 2010 and 2021 and have tissue or circulating tumor DNA-based next-generation sequencing results were enrolled. Short-form
APC
mutations were defined as those truncated at amino acid 1,256 or shorter, lacking all seven 20-amino acid repeat (20-AAR) regions. Non-short-form
APC
mutations were defined as those possess more than one 20-AAR. Short-form and non-short-form heterozygous mutations were classified as non-short-form
APC
mutations. We confirmed incidence of mCRC with short-form
APC
mutations and compared clinicopathological characteristics and overall survival (OS) between mCRC patients with short-form and non-short-form
APC
mutations.
Results:
Of 177 patients (median age, 56.0 years) included in this study, 44 (25%) and 79 (45%) had short-form and non-short-form APC mutations, respectively. Patients with short-form
APC
mutations were not likely to have lung metastasis (P = 0.15). Logistic regression multivariate analysis, lung metastasis was related to mCRC patients with short-form APC mutations (Odds ratio: 0.46, P = 0.047). Patients with short-form APC mutations had significantly shorter overall survival (OS) than did those without (n = 133), with a median OS of 34.7 vs 50.5 months (
P
Log-rank
= 0.035, hazard ratio (HR), 1.59; 95% confidence interval (CI), 1.03-2.45). In multivariate analysis, short-form
APC
mutation was independent factor related to OS (hazard ratio (HR): 1.68, P = 0.02), as well as the
BRAF
V600E mutation, liver metastasis and peritoneal metastasis.
Conclusions:
Short-form
APC
mutation is more common in mCRC patients without lung metastases and is independently associated with a short prognosis.
1 organization
1 drug
2 targets
Target
β-cateninTarget
APC