Intra-Abdominal Sporadic Desmoid Tumors with Canonical CTNNB1 and Uncommon Wnt/β-Catenin Pathway Somatic Mutations-A Clinicopathologic and Genetic Study of Five Cases.
- 1Department of Pathology, Caritas Medical Center, Wing Hong Street, Kowloon, Hong Kong.
- 2Department of Pathology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510163, China.
Abstract
Desmoid tumors (DTs) may be sporadic or associated with familial polyposis syndromes, including familial adenomatous polyposis (FAP) and its variant, Gardner syndrome (GS). DTs are pathogenetically linked to activation of the Wnt/β-catenin signaling pathway. In sporadic DT, CTNNB1 is most frequently implicated, with exon 3 somatic mutations (T41A, S45F and S45P) being the most commonly reported. APC is implicated in FAP/GS-associated DTs and occasionally in sporadic DT, most often through alterations involving the exon 15 mutation cluster region. In this study of five sporadic intra-abdominal DTs, we identified uncommon somatic missense mutations in three cases involving APC (exons 2 and 13), LRP6 (exon 3) and TCF7L2 (exons 3, 6, 8 and 10). One case harbored the canonical activating CTNNB1 exon 3 p.S45P mutation, whereas another one case showed no detectable genomic alterations. Multi-algorithm in silico assessment using AlphaMissense, REVEL, CADD, SIFT and PolyPhen-2 provided supportive computational evidence for potential functional effects of several variants, particularly TCF7L2 p.P113L, p.R243W and p.C337Y, and CTNNB1 p.S45P, while predictions were variable for other variants. All five tumors arose intra-abdominally and presented as abdominal emergencies requiring surgical intervention. During a median follow-up of 24 months (range, 18-68 months), four patients remained recurrence-free, whereas one case developed multifocal intra-abdominal recurrence approximately five years after the initial resection and underwent repeat surgery. These findings broaden the spectrum of Wnt/β-catenin pathway alterations observed in intra-abdominal DTs, although the functional consequences of the uncommon variants require experimental validation.
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BibTeX
@article{ng2026intraabdominal,
title = {{Intra-Abdominal Sporadic Desmoid Tumors with Canonical CTNNB1 and Uncommon Wnt/β-Catenin Pathway Somatic Mutations-A Clinicopathologic and Genetic Study of Five Cases.}},
author = {Chi Sing Ng and Jilong Qin and Gloria Y Gao},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198655},
url = {https://europepmc.org/article/MED/42883903},
note = {CC BY},
}
RIS
TY - JOUR
TI - Intra-Abdominal Sporadic Desmoid Tumors with Canonical CTNNB1 and Uncommon Wnt/β-Catenin Pathway Somatic Mutations-A Clinicopathologic and Genetic Study of Five Cases.
AU - Chi Sing Ng
AU - Jilong Qin
AU - Gloria Y Gao
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198655
UR - https://europepmc.org/article/MED/42883903
AB - Desmoid tumors (DTs) may be sporadic or associated with familial polyposis syndromes, including familial adenomatous polyposis (FAP) and its variant, Gardner syndrome (GS). DTs are pathogenetically linked to activation of the Wnt/β-catenin signaling pathway. In sporadic DT, CTNNB1 is most frequently implicated, with exon 3 somatic mutations (T41A, S45F and S45P) being the most commonly reported. APC is implicated in FAP/GS-associated DTs and occasionally in sporadic DT, most often through alterations involving the exon 15 mutation cluster region. In this study of five sporadic intra-abdominal DTs, we identified uncommon somatic missense mutations in three cases involving APC (exons 2 and 13), LRP6 (exon 3) and TCF7L2 (exons 3, 6, 8 and 10). One case harbored the canonical activating CTNNB1 exon 3 p.S45P mutation, whereas another one case showed no detectable genomic alterations. Multi-algorithm in silico assessment using AlphaMissense, REVEL, CADD, SIFT and PolyPhen-2 provided supportive computational evidence for potential functional effects of several variants, particularly TCF7L2 p.P113L, p.R243W and p.C337Y, and CTNNB1 p.S45P, while predictions were variable for other variants. All five tumors arose intra-abdominally and presented as abdominal emergencies requiring surgical intervention. During a median follow-up of 24 months (range, 18-68 months), four patients remained recurrence-free, whereas one case developed multifocal intra-abdominal recurrence approximately five years after the initial resection and underwent repeat surgery. These findings broaden the spectrum of Wnt/β-catenin pathway alterations observed in intra-abdominal DTs, although the functional consequences of the uncommon variants require experimental validation.
SN - 1422-0067
ER -