Skin biopsy or two T25 flasks of cultured fibroblasts from skin*
Blood – 2-3 mL in an EDTA (purple top) tube.
Bone Marrow - 2-3 mL in an EDTA (purple top) tube.
Saliva – please contact the lab regarding the availability of collection kits by emailing DGDGeneticCounselor@chop.edu.
DNA – 3 ug of DNA with a concentration of at least 50 ng/ul
*If the individual being tested has suspected or confirmed myelodysplasia or leukemia/lymphoma, or if the individual is the recipient of a donor (allogeneic) bone marrow transplant, cultured fibroblasts from skin are the preferred specimen to assess for constitutional genetic variants. Bone marrow, blood, and saliva can harbor cells with somatic variants due to underlying processes related to bone marrow failure. Therefore, when testing these specimens, it’s possible that it will be uncertain if an identified variant is constitutional/germline or acquired. These samples can only be accepted for constitutional genetic testing related to a clinical indication of bone marrow failure if the patients are proven to have no active malignancy.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Clinical Features
The Comprehensive Bone Marrow Failure (BMF)/Myelodysplastic Syndrome (MDS)/Leukemia Predisposition Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited myelodysplastic syndromes, leukemia and bone marrow failure.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday through Friday 9:00am - 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. However, based on a recent study, pathogenic variants in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients by massively parallel sequencing. In addition, 18.1% of patients with unclassified inherited bone marrow failure syndromes were found to carry germline pathogenic variants in CXCR4, GATA2, G6PC3, MAST, MYH9, RPL5, RTEL1, TERT, TERC, TINF2, or WAS genes [PMID: 27418648]. Another recent study identified GATA2 pathogenic germline variants in 7% of children and adolescents with de novo MDS [PMID: 26702063].
Estimated detection rates may differ depending whether the proband meets the clinical diagnostic criteria for specific cancer predisposition syndromes mentioned above. Estimated detection rates for certain syndromes are as follows:
Identification of an underlying genetic cause is critical in establishing an inherited versus acquired etiology for bone marrow failure, which in turn has profound impacts on patient management and genetic counseling for families of affected patients. Myelodysplastic syndrome and secondary leukemia are rare in children and young adults. The occurrence of these disorders in these age groups is increasingly associated with inherited pathogenic variants in genes associated with familial cancer predisposition. Such predisposition syndromes may also be associated with sensitivity to cytotoxic anti-cancer therapy.
Next generation sequencing: Genomic DNA was extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing was performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis were based on the GRCh38 reference sequence. Sequencing data was processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Comprehensive Bone Marrow Failure (BMF)/Myelodysplastic Syndrome (MDS)/Leukemia Predisposition Panel includes sequence and copy number analysis of the following genes: ABCB7, ACD, AK2, ALAS2, ANKRD26*, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1, CBL*, CDAN1, CDIN1, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1,CXCR4*, DDX11, DDX41, DKC1, ELANE*, EPCAM**, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, G6PC3, GATA1, GATA2, GFI1*, GLRX5, HAX1, KIF23, KLF1, KRAS*, LAMTOR2, LIG4, LYST, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11*, RAB27A, RAC2*, RAD51, RAD51C, RAF1*, RBM8A, RECQL, RMRP, RPL11, RPL15, RPL19, RPL26, RPL27, RPL35A, RPL5, RPS10, RPS17, RPS19, RPS24, RPS26, RPS27, RPS29, RPS7, RTEL1, RUNX1, SAMD9*, SAMD9L*, SBDS, SEC23B, SH2B3, SLC25A38, SLC37A4, SLX4, SOS1*, SRP72, TAFAZZIN, TERC, TERT, TINF2, TP53, USB1, VPS13B, VPS45, WAS, WIPF1, WRAP53
* Sequence analysis only is performed for these genes.
** Copy number analysis only is performed for these genes.
CPT Codes
81441
Collection
Collect
Skin biopsy or two T25 flasks of cultured fibroblasts from skin*
Blood – 2-3 mL in an EDTA (purple top) tube.
Bone Marrow - 2-3 mL in an EDTA (purple top) tube.
Saliva – please contact the lab regarding the availability of collection kits by emailing DGDGeneticCounselor@chop.edu.
DNA – 3 ug of DNA with a concentration of at least 50 ng/ul
*If the individual being tested has suspected or confirmed myelodysplasia or leukemia/lymphoma, or if the individual is the recipient of a donor (allogeneic) bone marrow transplant, cultured fibroblasts from skin are the preferred specimen to assess for constitutional genetic variants. Bone marrow, blood, and saliva can harbor cells with somatic variants due to underlying processes related to bone marrow failure. Therefore, when testing these specimens, it’s possible that it will be uncertain if an identified variant is constitutional/germline or acquired. These samples can only be accepted for constitutional genetic testing related to a clinical indication of bone marrow failure if the patients are proven to have no active malignancy.
Specimen Preparation
Please provide detailed clinical history and features. For more information contact the lab at 6-1447 or by sending an email to DGDGeneticCounselor@chop.edu.
Unacceptable Conditions
Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.
Storage/Transport Temperature
Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.
Volume Required
2-3 mL of blood or 3 ug of DNA with a concentration of at least 50 ng/ul
Minimum Required
1 mL of whole blood
Phlebotomy Draw
Yes
Ordering
Clinical Features
The Comprehensive Bone Marrow Failure (BMF)/Myelodysplastic Syndrome (MDS)/Leukemia Predisposition Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited myelodysplastic syndromes, leukemia and bone marrow failure.
Performing Lab
Division of Genomic Diagnostics
Performed
Monday through Friday 9:00am - 4:00pm
Reported
28 days
Detection Rate
The diagnostic yield for comprehensive NGS panels is not yet well-established, and depends on the panel's gene content and the patient's clinical features. However, based on a recent study, pathogenic variants in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients by massively parallel sequencing. In addition, 18.1% of patients with unclassified inherited bone marrow failure syndromes were found to carry germline pathogenic variants in CXCR4, GATA2, G6PC3, MAST, MYH9, RPL5, RTEL1, TERT, TERC, TINF2, or WAS genes [PMID: 27418648]. Another recent study identified GATA2 pathogenic germline variants in 7% of children and adolescents with de novo MDS [PMID: 26702063].
Estimated detection rates may differ depending whether the proband meets the clinical diagnostic criteria for specific cancer predisposition syndromes mentioned above. Estimated detection rates for certain syndromes are as follows:
Identification of an underlying genetic cause is critical in establishing an inherited versus acquired etiology for bone marrow failure, which in turn has profound impacts on patient management and genetic counseling for families of affected patients. Myelodysplastic syndrome and secondary leukemia are rare in children and young adults. The occurrence of these disorders in these age groups is increasingly associated with inherited pathogenic variants in genes associated with familial cancer predisposition. Such predisposition syndromes may also be associated with sensitivity to cytotoxic anti-cancer therapy.
Next generation sequencing: Genomic DNA was extracted from patient tissue following standard DNA extraction protocols. Whole genome sequencing was performed on the Illumina NovaSeq 6000 platform using the Illumina DNA PCR-Free Library Prep with 150bp paired-end reads. Mapping and analysis were based on the GRCh38 reference sequence. Sequencing data was processed using the Dragen pipeline (Illumina) to call both sequence and copy number variants.
Molecular Testing Notes
The Comprehensive Bone Marrow Failure (BMF)/Myelodysplastic Syndrome (MDS)/Leukemia Predisposition Panel includes sequence and copy number analysis of the following genes: ABCB7, ACD, AK2, ALAS2, ANKRD26*, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1, CBL*, CDAN1, CDIN1, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1,CXCR4*, DDX11, DDX41, DKC1, ELANE*, EPCAM**, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, G6PC3, GATA1, GATA2, GFI1*, GLRX5, HAX1, KIF23, KLF1, KRAS*, LAMTOR2, LIG4, LYST, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11*, RAB27A, RAC2*, RAD51, RAD51C, RAF1*, RBM8A, RECQL, RMRP, RPL11, RPL15, RPL19, RPL26, RPL27, RPL35A, RPL5, RPS10, RPS17, RPS19, RPS24, RPS26, RPS27, RPS29, RPS7, RTEL1, RUNX1, SAMD9*, SAMD9L*, SBDS, SEC23B, SH2B3, SLC25A38, SLC37A4, SLX4, SOS1*, SRP72, TAFAZZIN, TERC, TERT, TINF2, TP53, USB1, VPS13B, VPS45, WAS, WIPF1, WRAP53
* Sequence analysis only is performed for these genes.
** Copy number analysis only is performed for these genes.
