Purpose Cancer predisposition syndromes are genetic disorders that significantly raise the risk of developing malignancies.Although the malignant manifestations of cancer predisposition syndromes are well-studied,reco...Purpose Cancer predisposition syndromes are genetic disorders that significantly raise the risk of developing malignancies.Although the malignant manifestations of cancer predisposition syndromes are well-studied,recognizing their non-malignant features is crucial for early diagnosis,especially in children and adolescents.Methods A comprehensive literature search was conducted using the PubMed database,focusing on non-malignant manifestations of cancer predisposition syndromes in children and adolescents.Key sources included the Clinical Cancer Research pediatric oncology series and ORPHANET.Studies that described clinical signs and symptoms affecting specific organ systems were included.Results Non-malignant dermatological features often serve as early indicators of cancer predisposition syndromes,including café-au-lait spots in Neurofibromatosis Type 1 and facial angiofibromas in Tuberous Sclerosis Complex.Neurological and developmental anomalies such as cerebellar ataxia in ataxia-telangiectasia and intellectual disabilities in neurofibromatosis type 1 and tuberous sclerosis complex are significant indicators.Growth and metabolic anomalies are also notable,including overgrowth in Beckwith–Wiedemann syndrome and growth hormone deficiency in neurofibromatosis Type 1.In addition,facial anomalies,ocular manifestations,hearing issues,and thyroid anomalies are prevalent across various cancer predisposition syndromes.For instance,hearing loss may be significant in neurofibromatosis Type 2,while thyroid nodules are common in PTEN hamartoma tumor syndrome and DICER1 syndrome.Cardiovascular,abdominal,musculoskeletal,pulmonary,genitourinary manifestations,and prenatal deviations further complicate the clinical picture.Conclusions Recognizing non-malignant features of cancer predisposition syndromes is essential for early diagnosis and management.This organ-specific overview furthers awareness among healthcare providers,facilitating timely genetic counseling,surveillance programs,and preventive measures,ultimately improving patient outcomes.展开更多
The etiology of childhood cancer remains largely unknown.Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis.Unlike adult cancers,pediatric cancers typically have a higher ...The etiology of childhood cancer remains largely unknown.Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis.Unlike adult cancers,pediatric cancers typically have a higher prevalence of germline pathogenic variants in cancer predisposition genes.Inherited cancer predisposition syndromes account for approximately 10%of all childhood cancers.Over the years,the diagnosis of cancer predisposition syndromes was based on clinical suspicion prompting referral to a specialized geneticist.However,advances in molecular technologies have led to a shift toward a“genotypefirst”approach.Identification of genetic variants related to cancer predisposition enables tailored treatment,improves clinical outcome,optimizes surveillance,and facilitates genetic counseling of the affected child and the family.展开更多
Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).He...Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity;in addition,there are several dozen less frequent types of familial tumors.The development of the majority albeit not all hereditary malignancies involves two-hit mechanism,i.e.the somatic inactivation of the remaining copy of the affected gene.Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes;however,population-based investigations and especially large-scale next-generation sequencing data sets demonstrate that the presence of some highly-penetrant PVs is often compatible with healthy status.Hereditary cancer research initially focused mainly on cancer detection and prevention.Recent studies identified multiple HCS-specific drug vulnerabilities,which translated into the development of highly efficient therapeutic options.展开更多
The usage of next-generation sequencing(NGS)to detect copy number variation(CNV)is widely accepted in cancer research.Based on an AluScanCNV software developed by us previously,an AluScanCNV2 software has been develop...The usage of next-generation sequencing(NGS)to detect copy number variation(CNV)is widely accepted in cancer research.Based on an AluScanCNV software developed by us previously,an AluScanCNV2 software has been developed in the present study as an R package that performs CNV detection from NGS data obtained through AluScan,wholegenome sequencing or other targeted NGS platforms.Its applications would include the expedited usage of somatic CNVs for cancer subtyping,and usage of recurrent germline CNVs to perform machine learning-assisted prediction of a test subject’s susceptibility to cancer.展开更多
Soft tissue sarcoma(STS)most often occurs sporadically,but can also arise in the setting of a germline cancer predisposition syndrome(CPS).There is significant diversity amongst STS diagnoses as these tumors exhibit a...Soft tissue sarcoma(STS)most often occurs sporadically,but can also arise in the setting of a germline cancer predisposition syndrome(CPS).There is significant diversity amongst STS diagnoses as these tumors exhibit a variety of histologies,occur in all age groups,and can occur in any location in the body.This diversity is also reflected in the many known associated germline cancer predisposition associations.Some STS diagnoses,such as anaplastic rhabdomyosarcoma,are associated with high heritability and other STS,such as Ewing sarcoma,are notably absent from known CPS.Recognizing when a STS is more likely to be hereditary can influence clinical management.Individuals diagnosed with STS due to CPS may be at risk for other malignancies and should undergo additional surveillance for early detection.Additionally,family members should undergo genetic testing as they also may be at risk to develop STS and other CPS-associated malignancies.Some underlying cancer predisposition diagnoses may have implications for the treatment of a concurrent malignancy as in the case of PARP inhibitor therapy in the setting of homologous recombination deficiency.This review summarizes current knowledge of selected STS and their associations with CPS.展开更多
基金The research of KM on pediatric cancer predisposition is supported by Deutsche Krebshilfe(70115888)Deutsche Forschungsgemeinschaft(KU3764/3-1)intramurale Forschungsförderung,University of Augsburg,Germany.FMC’s research on rhabdoid tumor disposition is supported by Deutsche Krebshilfe 70113981.
文摘Purpose Cancer predisposition syndromes are genetic disorders that significantly raise the risk of developing malignancies.Although the malignant manifestations of cancer predisposition syndromes are well-studied,recognizing their non-malignant features is crucial for early diagnosis,especially in children and adolescents.Methods A comprehensive literature search was conducted using the PubMed database,focusing on non-malignant manifestations of cancer predisposition syndromes in children and adolescents.Key sources included the Clinical Cancer Research pediatric oncology series and ORPHANET.Studies that described clinical signs and symptoms affecting specific organ systems were included.Results Non-malignant dermatological features often serve as early indicators of cancer predisposition syndromes,including café-au-lait spots in Neurofibromatosis Type 1 and facial angiofibromas in Tuberous Sclerosis Complex.Neurological and developmental anomalies such as cerebellar ataxia in ataxia-telangiectasia and intellectual disabilities in neurofibromatosis type 1 and tuberous sclerosis complex are significant indicators.Growth and metabolic anomalies are also notable,including overgrowth in Beckwith–Wiedemann syndrome and growth hormone deficiency in neurofibromatosis Type 1.In addition,facial anomalies,ocular manifestations,hearing issues,and thyroid anomalies are prevalent across various cancer predisposition syndromes.For instance,hearing loss may be significant in neurofibromatosis Type 2,while thyroid nodules are common in PTEN hamartoma tumor syndrome and DICER1 syndrome.Cardiovascular,abdominal,musculoskeletal,pulmonary,genitourinary manifestations,and prenatal deviations further complicate the clinical picture.Conclusions Recognizing non-malignant features of cancer predisposition syndromes is essential for early diagnosis and management.This organ-specific overview furthers awareness among healthcare providers,facilitating timely genetic counseling,surveillance programs,and preventive measures,ultimately improving patient outcomes.
文摘The etiology of childhood cancer remains largely unknown.Recent evidence suggests that genetic factors play a substantial role in pediatric tumorigenesis.Unlike adult cancers,pediatric cancers typically have a higher prevalence of germline pathogenic variants in cancer predisposition genes.Inherited cancer predisposition syndromes account for approximately 10%of all childhood cancers.Over the years,the diagnosis of cancer predisposition syndromes was based on clinical suspicion prompting referral to a specialized geneticist.However,advances in molecular technologies have led to a shift toward a“genotypefirst”approach.Identification of genetic variants related to cancer predisposition enables tailored treatment,improves clinical outcome,optimizes surveillance,and facilitates genetic counseling of the affected child and the family.
基金Supported by The Russian Science Foundation,No.17-75-30027。
文摘Hereditary cancer syndromes(HCSs)are arguably the most frequent category of Mendelian genetic diseases,as at least 2%of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants(PVs).Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity;in addition,there are several dozen less frequent types of familial tumors.The development of the majority albeit not all hereditary malignancies involves two-hit mechanism,i.e.the somatic inactivation of the remaining copy of the affected gene.Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes;however,population-based investigations and especially large-scale next-generation sequencing data sets demonstrate that the presence of some highly-penetrant PVs is often compatible with healthy status.Hereditary cancer research initially focused mainly on cancer detection and prevention.Recent studies identified multiple HCS-specific drug vulnerabilities,which translated into the development of highly efficient therapeutic options.
基金The study was supported by grants to H.Xue from University Grants Committee(VPRDO09/10.SC08)Innovation and Technology Fund(ITS/113/15FP)of Hong Kong SAR.
文摘The usage of next-generation sequencing(NGS)to detect copy number variation(CNV)is widely accepted in cancer research.Based on an AluScanCNV software developed by us previously,an AluScanCNV2 software has been developed in the present study as an R package that performs CNV detection from NGS data obtained through AluScan,wholegenome sequencing or other targeted NGS platforms.Its applications would include the expedited usage of somatic CNVs for cancer subtyping,and usage of recurrent germline CNVs to perform machine learning-assisted prediction of a test subject’s susceptibility to cancer.
基金This manuscript utilized the Genetic Counseling Shared Resource at Huntsman Cancer Institute at the University of Utah and was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014JDS holds the Helen Clise Presidential Endowed Chair in Li Fraumeni Syndrome Research(University of Utah)and is the Co-Founder/CEO of Peel Therapeutics,Inc.
文摘Soft tissue sarcoma(STS)most often occurs sporadically,but can also arise in the setting of a germline cancer predisposition syndrome(CPS).There is significant diversity amongst STS diagnoses as these tumors exhibit a variety of histologies,occur in all age groups,and can occur in any location in the body.This diversity is also reflected in the many known associated germline cancer predisposition associations.Some STS diagnoses,such as anaplastic rhabdomyosarcoma,are associated with high heritability and other STS,such as Ewing sarcoma,are notably absent from known CPS.Recognizing when a STS is more likely to be hereditary can influence clinical management.Individuals diagnosed with STS due to CPS may be at risk for other malignancies and should undergo additional surveillance for early detection.Additionally,family members should undergo genetic testing as they also may be at risk to develop STS and other CPS-associated malignancies.Some underlying cancer predisposition diagnoses may have implications for the treatment of a concurrent malignancy as in the case of PARP inhibitor therapy in the setting of homologous recombination deficiency.This review summarizes current knowledge of selected STS and their associations with CPS.
