Collect

Blood sample in an EDTA (purple-top) tube.

Storage/Transport Temperature

Room Temp

Performed

Monday through Friday 9:00am - 4:00pm

Volume Required

3-5 ml

Minimum Required

1.5 ml

Phlebotomy Draw

Yes

Performed

Monday through Friday 9:00am - 4:00pm

Methodology

Seventy-three genes known to be associated with predisposition to MDS/leukemia are analyzed using Next Generation Sequence (NGS) technology. All coding exons of the 73 genes and 20 base pairs of 5' and 3' flanking intronic sequences are analyzed. All known intronic mutations of these genes are also evaluated. Pathogenic/likely pathogenic variants detected by NGS are confirmed by Sanger sequencing.
The panel also evaluates gross copy number variations of these genes by analyzing NGS data. Pathogenic/likely pathogenic CNVs detected by NGS are confirmed by MLPA and/or ddPCR. Certain genes or exons may not be evaluated for gross copy number variations, such as genes with no known gross deletion/duplication mutations, or genes or exons with pseudogenes or highly homologous sequences in the genome.

Reported

42 days

Synonyms

  • MDSLP
  • ACD, AK2, ANKRD26, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1 (FANCJ), CBL, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1, DDX11, DDX41, DKC1, EPCAM, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GATA1, GATA2, KRAS, LIG4, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11, RAD51, RAD51C, RAF1, RECQL, RMRP, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SH2B3, SLX4, SOS1, SRP72, TERC, TERT, TINF2, TP53, WAS, WIPF1, and WRAP53

LIS Mnemonic

MDSLP

Performed By

Division of Genomic Diagnostics

Available STAT

No

Clinical Features

The Hereditary MDS/Leukemia Predisposition Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited myelodysplastic syndromes (MDS) and leukemia. Inherited predisposition to hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and bone marrow myelodysplastic syndrome (MDS)] may be isolated or in association with syndromic features. MDS and AML may present as part of known bone marrow failure syndromes (eg. dyskeratosis congenita, severe congenital neutropenia, Fanconi anemia). Other hereditary cancer predisposition syndromes associated with leukemia include Li-Fraumeni syndrome, ataxia telangiectasia, Bloom syndrome, neurofibromatosis type 1, Noonan syndrome, or mismatch-repair deficiency syndrome. 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 (at least 73 at present time) associated with familial cancer predisposition. Such predisposition syndromes may also be associated with sensitivity to cytotoxic anti-cancer therapy, and thus identification of underlying genetic predisposition may not only impact family screening, but also may directly impact therapeutic approaches.

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, approximately 29% of families with inherited susceptibility to MDS/AML have pathogenic variants in the known predisposition genes [PMID: 26492932].

Estimated detection rates may differ depending whether the proband meets the clinical diagnostic criteria for specific cancer predisposition syndromes mentioned above.

Molecular Testing Notes

Conditions associated with predisposition to MDS/leukemia can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. The Hereditary MDS/Leukemia Predisposition Panel includes the following 73 genes: ACD, AK2, ANKRD26, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1 (FANCJ), CBL, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1, DDX11, DDX41, DKC1, EPCAM, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GATA1, GATA2, KRAS, LIG4, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11, RAD51, RAD51C, RAF1, RECQL, RMRP, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SH2B3, SLX4, SOS1, SRP72, TERC, TERT, TINF2, TP53, WAS, WIPF1, and WRAP53.

CPT Codes

81201, 81209, 81163, 81218, 81242, 81292, 81295, 81298, 81317, 81402, 81403, 81404, 81405 x 2, 81406 x 5, 81408 x 2, 81479, 81307
Collection

Collect

Blood sample in an EDTA (purple-top) tube.

Storage/Transport Temperature

Room Temp

Performed

Monday through Friday 9:00am - 4:00pm

Volume Required

3-5 ml

Minimum Required

1.5 ml

Phlebotomy Draw

Yes
Ordering

Performed

Monday through Friday 9:00am - 4:00pm

Methodology

Seventy-three genes known to be associated with predisposition to MDS/leukemia are analyzed using Next Generation Sequence (NGS) technology. All coding exons of the 73 genes and 20 base pairs of 5' and 3' flanking intronic sequences are analyzed. All known intronic mutations of these genes are also evaluated. Pathogenic/likely pathogenic variants detected by NGS are confirmed by Sanger sequencing.
The panel also evaluates gross copy number variations of these genes by analyzing NGS data. Pathogenic/likely pathogenic CNVs detected by NGS are confirmed by MLPA and/or ddPCR. Certain genes or exons may not be evaluated for gross copy number variations, such as genes with no known gross deletion/duplication mutations, or genes or exons with pseudogenes or highly homologous sequences in the genome.

Reported

42 days

Synonyms

  • MDSLP
  • ACD, AK2, ANKRD26, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1 (FANCJ), CBL, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1, DDX11, DDX41, DKC1, EPCAM, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GATA1, GATA2, KRAS, LIG4, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11, RAD51, RAD51C, RAF1, RECQL, RMRP, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SH2B3, SLX4, SOS1, SRP72, TERC, TERT, TINF2, TP53, WAS, WIPF1, and WRAP53

LIS Mnemonic

MDSLP

Performed By

Division of Genomic Diagnostics

Available STAT

No

Clinical Features

The Hereditary MDS/Leukemia Predisposition Panel is a next generation sequencing panel designed to identify underlying genetic variants associated with inherited myelodysplastic syndromes (MDS) and leukemia. Inherited predisposition to hematological malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and bone marrow myelodysplastic syndrome (MDS)] may be isolated or in association with syndromic features. MDS and AML may present as part of known bone marrow failure syndromes (eg. dyskeratosis congenita, severe congenital neutropenia, Fanconi anemia). Other hereditary cancer predisposition syndromes associated with leukemia include Li-Fraumeni syndrome, ataxia telangiectasia, Bloom syndrome, neurofibromatosis type 1, Noonan syndrome, or mismatch-repair deficiency syndrome. 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 (at least 73 at present time) associated with familial cancer predisposition. Such predisposition syndromes may also be associated with sensitivity to cytotoxic anti-cancer therapy, and thus identification of underlying genetic predisposition may not only impact family screening, but also may directly impact therapeutic approaches.

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, approximately 29% of families with inherited susceptibility to MDS/AML have pathogenic variants in the known predisposition genes [PMID: 26492932].

Estimated detection rates may differ depending whether the proband meets the clinical diagnostic criteria for specific cancer predisposition syndromes mentioned above.

Molecular Testing Notes

Conditions associated with predisposition to MDS/leukemia can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. The Hereditary MDS/Leukemia Predisposition Panel includes the following 73 genes: ACD, AK2, ANKRD26, APC, ATM, ATR, BLM, BRCA1, BRCA2, BRIP1 (FANCJ), CBL, CDKN2A, CEBPA, CHEK2, CSF3R, CTC1, DDX11, DDX41, DKC1, EPCAM, ERCC4, ESCO2, ETV6, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, GATA1, GATA2, KRAS, LIG4, MLH1, MPL, MSH2, MSH6, NBN, NF1, NF2, NHEJ1, NHP2, NOP10, PALB2, PARN, PAX5, PMS2, PTPN11, RAD51, RAD51C, RAF1, RECQL, RMRP, RTEL1, RUNX1, SAMD9, SAMD9L, SBDS, SH2B3, SLX4, SOS1, SRP72, TERC, TERT, TINF2, TP53, WAS, WIPF1, and WRAP53.
Result Interpretation
Administrative

CPT Codes

81201, 81209, 81163, 81218, 81242, 81292, 81295, 81298, 81317, 81402, 81403, 81404, 81405 x 2, 81406 x 5, 81408 x 2, 81479, 81307