TY - JOUR
T1 - Genetic testing and surveillance in infantile myofibromatosis
T2 - a report from the SIOPE Host Genome Working Group
AU - Hettmer, Simone
AU - Dachy, Guillaume
AU - Seitz, Guido
AU - Agaimy, Abbas
AU - Duncan, Catriona
AU - Jongmans, Marjolijn
AU - Hirsch, Steffen
AU - Kventsel, Iris
AU - Kordes, Uwe
AU - de Krijger, Ronald R.
AU - Metzler, Markus
AU - Michaeli, Orli
AU - Nemes, Karolina
AU - Poluha, Anna
AU - Ripperger, Tim
AU - Russo, Alexandra
AU - Smetsers, Stephanie
AU - Sparber-Sauer, Monika
AU - Stutz, Eveline
AU - Bourdeaut, Franck
AU - Kratz, Christian P.
AU - Demoulin, Jean Baptiste
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2021/10
Y1 - 2021/10
N2 - Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
AB - Infantile myofibromatosis (IM), which is typically diagnosed in young children, comprises a wide clinical spectrum ranging from inconspicuous solitary soft tissue nodules to multiple disseminated tumors resulting in life-threatening complications. Familial IM follows an autosomal dominant mode of inheritance and is linked to PDGFRB germline variants. Somatic PDGFRB variants were also detected in solitary and multifocal IM lesions. PDGFRB variants associated with IM constitutively activate PDGFRB kinase activity in the absence of its ligand. Germline variants have lower activating capabilities than somatic variants and, thus, require a second cis-acting hit for full receptor activation. Typically, these mutant receptors remain sensitive to tyrosine kinase inhibitors such as imatinib. The SIOPE Host Genome Working Group, consisting of pediatric oncologists, clinical geneticists and scientists, met in January 2020 to discuss recommendations for genetic testing and surveillance for patients who are diagnosed with IM or have a family history of IM/PDGFRB germline variants. This report provides a brief review of the clinical manifestations and genetics of IM and summarizes our interdisciplinary recommendations.
KW - Genetic counseling
KW - Infantile myofibromatosis
KW - PDGFRB variants
KW - Surveillance
UR - http://www.scopus.com/inward/record.url?scp=85090310300&partnerID=8YFLogxK
U2 - 10.1007/s10689-020-00204-2
DO - 10.1007/s10689-020-00204-2
M3 - Article
C2 - 32888134
AN - SCOPUS:85090310300
VL - 20
SP - 327
EP - 336
JO - Familial Cancer
JF - Familial Cancer
SN - 1389-9600
IS - 4
ER -