TY - JOUR
T1 - Biological Role and Clinical Implications of MYOD1L122R Mutation in Rhabdomyosarcoma
AU - Di Carlo, Daniela
AU - Chisholm, Julia
AU - Kelsey, Anna
AU - Alaggio, Rita
AU - Bisogno, Gianni
AU - Minard-Colin, Veronique
AU - Jenney, Meriel
AU - Dávila Fajardo, Raquel
AU - Merks, Johannes H.M.
AU - Shipley, Janet M.
AU - Selfe, Joanna L.
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Major progress in recent decades has furthered our clinical and biological understanding of rhabdomyosarcoma (RMS) with improved stratification for treatment based on risk factors. Clinical risk factors alone were used to stratify patients for treatment in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 protocol. The current EpSSG overarching study for children and adults with frontline and relapsed rhabdomyosarcoma (FaR-RMS NCT04625907) includes FOXO1 fusion gene status in place of histology as a risk factor. Additional molecular features of significance have recently been recognized, including the MYOD1L122R gene mutation. Here, we review biological information showing that MYOD1L122R blocks cell differentiation and has a MYC-like activity that enhances tumorigenesis and is linked to an aggressive cellular phenotype. MYOD1L122R mutations can be found together with mutations in other genes, such as PIK3CA, as potentially cooperating events. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ten publications in the clinical literature involving 72 cases were reviewed. MYOD1L122R mutation in RMS can occur in both adults and children and is frequent in sclerosing/spindle cell histology, although it is also significantly reported in a subset of embryonal RMS. MYOD1L122R mutated tumors most frequently arise in the head and neck and extremities and are associated with poor outcome, raising the issue of how to use MYOD1L122R in risk stratification and how to treat these patients most effectively.
AB - Major progress in recent decades has furthered our clinical and biological understanding of rhabdomyosarcoma (RMS) with improved stratification for treatment based on risk factors. Clinical risk factors alone were used to stratify patients for treatment in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 protocol. The current EpSSG overarching study for children and adults with frontline and relapsed rhabdomyosarcoma (FaR-RMS NCT04625907) includes FOXO1 fusion gene status in place of histology as a risk factor. Additional molecular features of significance have recently been recognized, including the MYOD1L122R gene mutation. Here, we review biological information showing that MYOD1L122R blocks cell differentiation and has a MYC-like activity that enhances tumorigenesis and is linked to an aggressive cellular phenotype. MYOD1L122R mutations can be found together with mutations in other genes, such as PIK3CA, as potentially cooperating events. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ten publications in the clinical literature involving 72 cases were reviewed. MYOD1L122R mutation in RMS can occur in both adults and children and is frequent in sclerosing/spindle cell histology, although it is also significantly reported in a subset of embryonal RMS. MYOD1L122R mutated tumors most frequently arise in the head and neck and extremities and are associated with poor outcome, raising the issue of how to use MYOD1L122R in risk stratification and how to treat these patients most effectively.
KW - MYOD1
KW - children
KW - high-risk
KW - sclerosing rhabdomyosarcoma
KW - spindle cell
UR - http://www.scopus.com/inward/record.url?scp=85151376107&partnerID=8YFLogxK
U2 - 10.3390/cancers15061644
DO - 10.3390/cancers15061644
M3 - Review article
AN - SCOPUS:85151376107
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 6
M1 - 1644
ER -