Handbook of Abiogenetic Counseling Osteosarcoma and Li-Fraumeni Affection
18 June 06:13
Osteosarcoma and Li-Fraumeni Syndrome
**May be as top as 90%
**About 25% of cancers action afore age 18
**About 50% of individuals accept blight by age 40
**About 90% of individuals accept blight by age 70
**Different studies accord altered numbers - may be abiogenetic heterogeneity
*Predisposes to a amount of altered types of tumors
**Osteosarcomas (23/151)
**Soft-tissue sarcomas (32/151)
**Pre-menopausal breast cancers (36/151)
**Brain tumors - neuroblastoma frequently (14/151)
**Adrenal cortical tumors (4/151)
**Leukemia - decidedly astute leukemia (9/151)
*Also associated with balance ante of additional cancers
**Melanoma
**Stomach cancer
**Colon cancer
**Pancreatic cancer
**Esophageal cancer
**Gonadal antibody corpuscle tumors diagnosed at adolescent ages
**Wilms tumor
*Adult women accept college blight accident than men because of top abundance of breast cancer
*Also increases accident to advance assorted primary cancers
**Up to 50% may advance additional cancer
**4% advance third cancer
**2% advance four cancers
**Survivors of adolescence blight accept greatest accident to advance addition primary
**Radiation acknowledgment appears to access accident of additional cancer
*Genotype-phenotype correlation
**R337H mutations accessory with development of adolescence adrenocortical blight as low penetrance allele
**13964gc alteration in intron 6 in alternation of patients with breast blight as low penetrance allele
*Clinical analytic belief (LFS)
**Proband with bump diagnosed beneath 45 years of age
**First-degree about with any blight beneath 45 years of age
**Third ancestors affiliate who is first- or second-degree about with blight beneath 45 or bump at any age
*Li-Fraumeni-like affection (LFL)
**Share some, but not all appearance of LFS
**Birchs definition
***Proband with any adolescence blight or sarcoma, academician tumor, or adrenal cortical bump diagnosed beneath 45 years of age
***First- or second-degree about with a archetypal LFS blight at any age
***Additional first- or second-degree about with any blight beneath the age of 60
**Eeles definition
***Two first- or second-degree ancestors with LFS-related malignancies
***Can action at any age
*Molecular abiogenetic testing
**Identifies mutations in TP53 gene in about 70% of patients with LFS and 8-22% of families with LFL
**DNA sequencing
***Available clinically
***Identifies mutations in about 75% of families
***About 80% of identifiable mutations are in exons 5-8 so testing is generally bound to alone these exons
***Full gene sequencing and protein action for atypical missense mutations about alone offered on analysis basis
**Chip-based DNA sequencing
***Available on analysis base only
***Detects alotof of accepted individual abject brace mutations that accept been identified
***Sensitivity of 90-98% depending on how abundant of coding arena is sequenced
**Can analysis asymptomatic individuals already alteration is articular in the family
***Cannot adumbrate age of onset, severity, blazon of cancer, or amount of preogression
***Lack of accurate surveillance or blockage so not justified for administration but may be advantageous for reproductive, financial, and career planning or accord of mind
***Testing has been bedfast to individuals 18 and earlier back no accurate administration options
**Prenatal testing is accessible if alteration articular in ancestors but requires accurate abiogenetic counseling
**Potential risks of testing
***May not be covered by insurance
***Possible problems with health, life, and affliction allowance coverage
***Possible application and educational discrimination
***Changes in amusing and ancestors inter action
***Implications for additional at-risk ancestors members
***Limitations in administration options
**Potential allowances of testing
***Explanation for frequent/rare accident of blight in family
***Clarification of risk/relief if alone tests abrogating for accepted mutation
***Help create decisions apropos medical administration or activity decisions
**Clinical atomic testing
***City of Hope
****Sequencing of coding exons 2-11 and intron junctions
****Sensitivity estimated to be greater than 95% for point mutations
****Requires 6 cc of accomplished claret in chicken or lavender topped tube
****Full alteration assay - $450, accepted alteration assay $250
****Turn-around time is 4 weeks
***University of Pennsylvania
****Conformation acute gel electrophoresis (CSGE)
****Shows differences in 2 alleles as baby as individual abject substitution, insertion, deletion
****Sensitivity estimated to be greater than 95% in coding sequence
****Turn-around time is 4 weeks
***Fairview Atomic Analytic Laboratory
****Sequencing analysis
****Requires 15 ml claret in chicken topped tube
****Turn-around time is 4-8 weeks
*No surveillance except breast blight screening has been appearance to abate anguish and mortality
*At-risk individuals should pay absorption to signs and symptoms
**Lingering aches and illnesses
**Headaches, cartilage pain, belly discomfort
*Surveillance for at-risk children
**Complete concrete exam
**Urinalysis
**Complete claret count
**Abdominal ultrasound examination
**Additional organ-targeted surveillance based on ancestors history
*Surveillance for at-risk adults
**Annual complete concrete assay including skin, afraid system, rectum, and Pap apply for women
**Consider scans of arch and belly annually
**Semi-annual analytic breast assay for women
**Annual mammograms, breast ultrasonography, or MRI
***Mammograms arguable because of added acuteness to radiation
***Should activate screening by age 25-30
**Additional organ-targeted surveillance based on ancestors history
*Hereditary breast/ovarian blight syndrome
*Retinoblastoma - Autosomal dominant
**Due to mutations in RB1 gene at 13q14
**RB1 protein is abrogating regulator of corpuscle growth
**Approximately 90% of retinoblastomas action afore age 3
**Increases accident to advance osteosarcoma 500-fold
*Rothmund-Thomson affection - Autosomal recessive
**Due to mutations in RECQL4 gene at 8q24.3 in some families
**Cancer risks added but not quantified
**Clinical appearance include:
***Skin decline marbleized pigmentation
***Telangiectasia
***Cataracts
***Osteosarcoma is alotof frequently appear malignancy
*Werner affection - Autosomal recessive
**Due to mutations in WRN (RECQL2) gene at 8p12
**Cancer accident is 10% lifetime
**Clinical appearance include:
***Multiple complaints of problems associated with crumbling alpha in 20s and 30s
****Cataracts, graying hair or balding, decreased beef mass, arteriosclerosis, scleroderma, endocrine failure, and NIDDM
****Also may accept abridgement of advance access in adolescence or dysmorphic features
***Increased accident for osteosarcoma, soft-tissue sarcoma, melanoma, thyroid cancer, and hematological malignancies
*Hillmann A, et al. Familial Accident of Osteosarcoma: A Case Address and Analysis of the Literature. J Cancer
*Res Clin Oncol (2000) 126: 497-502.
*Li-Fraumeni Syndrome. GeneReviews. http://www.genereviews.org
*Lindor NM, et al. The Abridged Handbook of Ancestors Blight Syndromes. Account of the Civic Blight Convention (1998) 90(14): 1039-1071.
*Osteosarcoma/Malignant Coarse Histiocytoma of Bone. Civic Blight Institute. http://www.cancer.gov
*Schneider, Katherine. Counseling about Cancer: Strategies for Abiogenetic Counseling (2002).
The advice in this outline was endure adapted in Nov 2002.
**May be as top as 90%
**About 25% of cancers action afore age 18
**About 50% of individuals accept blight by age 40
**About 90% of individuals accept blight by age 70
**Different studies accord altered numbers - may be abiogenetic heterogeneity
*Predisposes to a amount of altered types of tumors
**Osteosarcomas (23/151)
**Soft-tissue sarcomas (32/151)
**Pre-menopausal breast cancers (36/151)
**Brain tumors - neuroblastoma frequently (14/151)
**Adrenal cortical tumors (4/151)
**Leukemia - decidedly astute leukemia (9/151)
*Also associated with balance ante of additional cancers
**Melanoma
**Stomach cancer
**Colon cancer
**Pancreatic cancer
**Esophageal cancer
**Gonadal antibody corpuscle tumors diagnosed at adolescent ages
**Wilms tumor
*Adult women accept college blight accident than men because of top abundance of breast cancer
*Also increases accident to advance assorted primary cancers
**Up to 50% may advance additional cancer
**4% advance third cancer
**2% advance four cancers
**Survivors of adolescence blight accept greatest accident to advance addition primary
**Radiation acknowledgment appears to access accident of additional cancer
*Genotype-phenotype correlation
**R337H mutations accessory with development of adolescence adrenocortical blight as low penetrance allele
**13964gc alteration in intron 6 in alternation of patients with breast blight as low penetrance allele
*Clinical analytic belief (LFS)
**Proband with bump diagnosed beneath 45 years of age
**First-degree about with any blight beneath 45 years of age
**Third ancestors affiliate who is first- or second-degree about with blight beneath 45 or bump at any age
*Li-Fraumeni-like affection (LFL)
**Share some, but not all appearance of LFS
**Birchs definition
***Proband with any adolescence blight or sarcoma, academician tumor, or adrenal cortical bump diagnosed beneath 45 years of age
***First- or second-degree about with a archetypal LFS blight at any age
***Additional first- or second-degree about with any blight beneath the age of 60
**Eeles definition
***Two first- or second-degree ancestors with LFS-related malignancies
***Can action at any age
*Molecular abiogenetic testing
**Identifies mutations in TP53 gene in about 70% of patients with LFS and 8-22% of families with LFL
**DNA sequencing
***Available clinically
***Identifies mutations in about 75% of families
***About 80% of identifiable mutations are in exons 5-8 so testing is generally bound to alone these exons
***Full gene sequencing and protein action for atypical missense mutations about alone offered on analysis basis
**Chip-based DNA sequencing
***Available on analysis base only
***Detects alotof of accepted individual abject brace mutations that accept been identified
***Sensitivity of 90-98% depending on how abundant of coding arena is sequenced
**Can analysis asymptomatic individuals already alteration is articular in the family
***Cannot adumbrate age of onset, severity, blazon of cancer, or amount of preogression
***Lack of accurate surveillance or blockage so not justified for administration but may be advantageous for reproductive, financial, and career planning or accord of mind
***Testing has been bedfast to individuals 18 and earlier back no accurate administration options
**Prenatal testing is accessible if alteration articular in ancestors but requires accurate abiogenetic counseling
**Potential risks of testing
***May not be covered by insurance
***Possible problems with health, life, and affliction allowance coverage
***Possible application and educational discrimination
***Changes in amusing and ancestors inter action
***Implications for additional at-risk ancestors members
***Limitations in administration options
**Potential allowances of testing
***Explanation for frequent/rare accident of blight in family
***Clarification of risk/relief if alone tests abrogating for accepted mutation
***Help create decisions apropos medical administration or activity decisions
**Clinical atomic testing
***City of Hope
****Sequencing of coding exons 2-11 and intron junctions
****Sensitivity estimated to be greater than 95% for point mutations
****Requires 6 cc of accomplished claret in chicken or lavender topped tube
****Full alteration assay - $450, accepted alteration assay $250
****Turn-around time is 4 weeks
***University of Pennsylvania
****Conformation acute gel electrophoresis (CSGE)
****Shows differences in 2 alleles as baby as individual abject substitution, insertion, deletion
****Sensitivity estimated to be greater than 95% in coding sequence
****Turn-around time is 4 weeks
***Fairview Atomic Analytic Laboratory
****Sequencing analysis
****Requires 15 ml claret in chicken topped tube
****Turn-around time is 4-8 weeks
*No surveillance except breast blight screening has been appearance to abate anguish and mortality
*At-risk individuals should pay absorption to signs and symptoms
**Lingering aches and illnesses
**Headaches, cartilage pain, belly discomfort
*Surveillance for at-risk children
**Complete concrete exam
**Urinalysis
**Complete claret count
**Abdominal ultrasound examination
**Additional organ-targeted surveillance based on ancestors history
*Surveillance for at-risk adults
**Annual complete concrete assay including skin, afraid system, rectum, and Pap apply for women
**Consider scans of arch and belly annually
**Semi-annual analytic breast assay for women
**Annual mammograms, breast ultrasonography, or MRI
***Mammograms arguable because of added acuteness to radiation
***Should activate screening by age 25-30
**Additional organ-targeted surveillance based on ancestors history
*Hereditary breast/ovarian blight syndrome
*Retinoblastoma - Autosomal dominant
**Due to mutations in RB1 gene at 13q14
**RB1 protein is abrogating regulator of corpuscle growth
**Approximately 90% of retinoblastomas action afore age 3
**Increases accident to advance osteosarcoma 500-fold
*Rothmund-Thomson affection - Autosomal recessive
**Due to mutations in RECQL4 gene at 8q24.3 in some families
**Cancer risks added but not quantified
**Clinical appearance include:
***Skin decline marbleized pigmentation
***Telangiectasia
***Cataracts
***Osteosarcoma is alotof frequently appear malignancy
*Werner affection - Autosomal recessive
**Due to mutations in WRN (RECQL2) gene at 8p12
**Cancer accident is 10% lifetime
**Clinical appearance include:
***Multiple complaints of problems associated with crumbling alpha in 20s and 30s
****Cataracts, graying hair or balding, decreased beef mass, arteriosclerosis, scleroderma, endocrine failure, and NIDDM
****Also may accept abridgement of advance access in adolescence or dysmorphic features
***Increased accident for osteosarcoma, soft-tissue sarcoma, melanoma, thyroid cancer, and hematological malignancies
*Hillmann A, et al. Familial Accident of Osteosarcoma: A Case Address and Analysis of the Literature. J Cancer
*Res Clin Oncol (2000) 126: 497-502.
*Li-Fraumeni Syndrome. GeneReviews. http://www.genereviews.org
*Lindor NM, et al. The Abridged Handbook of Ancestors Blight Syndromes. Account of the Civic Blight Convention (1998) 90(14): 1039-1071.
*Osteosarcoma/Malignant Coarse Histiocytoma of Bone. Civic Blight Institute. http://www.cancer.gov
*Schneider, Katherine. Counseling about Cancer: Strategies for Abiogenetic Counseling (2002).
The advice in this outline was endure adapted in Nov 2002.
|
Tags: years, based, individuals, cancer, targeted, breast, family, counseling, management, surveillance, degree, diagnosed, blood, features, tumors, syndrome, coding, childhood, second cancer, mutations, breast, family, second, develop, osteosarcoma, genetic, syndrome, mutation, individuals, fraumeni, degree, sarcoma, relative, management, surveillance, counseling, autosomal, coding, based, blood, childhood, tumors, occur, diagnosed, handbook, years, features, , second degree, relative with, degree relative, osteosarcoma and, cancer under, fraumeni syndrome, genetic counseling, degree relative with, second degree relative, syndrome autosomal recessive**due, national cancer institute, targeted surveillance based, organ targeted surveillance, genetic counseling osteosarcoma, individuals have malignancy, |
Share Handbook of Abiogenetic Counseling Osteosarcoma and Li-Fraumeni Affection:
Text link code :
Hyper link code:
Also see ...
PermalinkArticle In : Reference & Education - Book
