TY - JOUR
T1 - Comprehensive molecular and clinicopathological profiling of desmoid tumours
AU - Kohsaka, Shinji
AU - Hirata, Makoto
AU - Ikegami, Masachika
AU - Ueno, Toshihide
AU - Kojima, Shinya
AU - Sakai, Tomohisa
AU - Ito, Kan
AU - Naka, Norifumi
AU - Ogura, Koichi
AU - Kawai, Akira
AU - Iwata, Shintaro
AU - Okuma, Tomotake
AU - Yonemoto, Tsukasa
AU - Kobayashi, Hiroshi
AU - Suehara, Yoshiyuki
AU - Hiraga, Hiroaki
AU - Kawamoto, Teruya
AU - Motoi, Toru
AU - Oda, Yoshinao
AU - Matsubara, Daisuke
AU - Matsuda, Koichi
AU - Nishida, Yoshihiro
AU - Mano, Hiroyuki
N1 - Funding Information:
This study was financially supported in part through grants from the Program for Integrated Database of Clinical and Genomic Information under Grant Number JP18kk0205003, the Project for Cancer Research And Therapeutic Evolution (P-CREATE) under the Grant Number JP19cm0106502, and for the Practical Research for Innovative Cancer Control under Grant Number JP19ck0106252 from the Japan Agency for Medical Research, and Development ( AMED ). This work was also supported in part by a grant from Eisai Co., Ltd.
Funding Information:
This study was financially supported in part through grants from the Program for Integrated Database of Clinical and Genomic Information under Grant Number JP18kk0205003, the Project for Cancer Research And Therapeutic Evolution (P-CREATE) under the Grant Number JP19cm0106502, and for the Practical Research for Innovative Cancer Control under Grant Number JP19ck0106252 from the Japan Agency for Medical Research, and Development (AMED). This work was also supported in part by a grant from Eisai Co., Ltd.
Publisher Copyright:
© 2020 The Author(s)
PY - 2021/3
Y1 - 2021/3
N2 - Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56–94.2; p = 8.0 × 106). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.
AB - Previous studies have not clearly identified a prognostic factor for desmoid tumours (DT). Whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) were performed in 64 cases of DT to investigate the molecular profiles in combination with the clinicopathological characteristics. CTNNB1 mutations with specific hotspots were identified in 56 cases (87.5%). A copy number loss in chromosome 6 (chr6) was identified in 14 cases (21.9%). Clustering based on the mRNA expression profiles was predictive of the patients' prognoses. The risk score generated by the expression of a three-gene set (IFI6, LGMN, and CKLF) was a strong prognostic marker for recurrence-free survival (RFS) in our cohort. In risk groups stratified by the expression of IFI6, the hazard ratio for recurrence-free survival in the high-risk group relative to the low-risk group was 12.12 (95% confidence interval: 1.56–94.2; p = 8.0 × 106). In conclusion, CTNNB1 mutations and a chr6 copy number loss are likely the causative mutations underlying the tumorigenesis of DT while the gene expression profiles may help to differentiate patients who would be good candidates for wait-and-see management and those who might benefit from additional systemic or radiation therapies.
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U2 - 10.1016/j.ejca.2020.12.001
DO - 10.1016/j.ejca.2020.12.001
M3 - Article
C2 - 33444924
AN - SCOPUS:85099174267
SN - 0959-8049
VL - 145
SP - 109
EP - 120
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
