Clarifications regarding the role of GPC3 in pleuropulmonary blastoma
- 1Department of Human Genetics, Medicine, McGill University
Abstract
In their publication, Zeng et al. propose that a germline variant in GPC3 (c.359G > A, p.R120H) may contribute to pleuropulmonary blastoma (PPB). We note the following − (1) the family described in the article harbors a germline pathogenic variant in DICER1, a well-established cause of PPB. This finding alone could explain the clinical presentation without invoking a role for GPC3. (2) The authors’ description of the GPC3 carrier status is inaccurate, as the gene’s X-linked inheritance makes the reported paternal genotype biologically impossible. (3) The GPC3 genotypes of other relatives are not reported, further limiting their conclusions. (4) The GPC3 variant is classified as a variant of uncertain significance and listed as likely benign in ClinVar, with no functional evidence linking it to PPB. (5) Pathogenic GPC3 variants cause Simpson-Golabi-Behmel syndrome, characterized by overgrowth and congenital anomalies which were not found in the reported family. While overexpression of glypican-3 has been associated with poor prognosis in several embryonal tumors, there is no proof that germline GPC3 variants drive PPB development. Misclassification of such variants could cause anxiety and unnecessary surveillance. Taken together, there is insufficient evidence to implicate the GPC3 variant in PPB.
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BibTeX
@article{pelletier2026clarifications,
title = {{Clarifications regarding the role of GPC3 in pleuropulmonary blastoma}},
author = {Dylan Pelletier and William D. Foulkes},
journal = {Discover Oncology},
year = {2026},
month = oct,
doi = {10.1007/s12672-026-06081-y},
url = {https://doi.org/10.1007/s12672-026-06081-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Clarifications regarding the role of GPC3 in pleuropulmonary blastoma
AU - Dylan Pelletier
AU - William D. Foulkes
PY - 2026
DA - 2026/10/25
JO - Discover Oncology
DO - 10.1007/s12672-026-06081-y
UR - https://doi.org/10.1007/s12672-026-06081-y
AB - In their publication, Zeng et al. propose that a germline variant in GPC3 (c.359G > A, p.R120H) may contribute to pleuropulmonary blastoma (PPB). We note the following − (1) the family described in the article harbors a germline pathogenic variant in DICER1, a well-established cause of PPB. This finding alone could explain the clinical presentation without invoking a role for GPC3. (2) The authors’ description of the GPC3 carrier status is inaccurate, as the gene’s X-linked inheritance makes the reported paternal genotype biologically impossible. (3) The GPC3 genotypes of other relatives are not reported, further limiting their conclusions. (4) The GPC3 variant is classified as a variant of uncertain significance and listed as likely benign in ClinVar, with no functional evidence linking it to PPB. (5) Pathogenic GPC3 variants cause Simpson-Golabi-Behmel syndrome, characterized by overgrowth and congenital anomalies which were not found in the reported family. While overexpression of glypican-3 has been associated with poor prognosis in several embryonal tumors, there is no proof that germline GPC3 variants drive PPB development. Misclassification of such variants could cause anxiety and unnecessary surveillance. Taken together, there is insufficient evidence to implicate the GPC3 variant in PPB.
SN - 2730-6011
ER -