Diagnostics

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Leukemia Panel

The Leukemia Panel is a comprehensive next-generation sequencing (NGS) panel that analyzes genes associated with increased risks for hereditary leukemia.

Leukemia affects approximately 1.5% of individuals in their lifetime (SEERP). Although the majority of leukemia is not related to heritable factors, some cases are related to heritable factors. Individuals who carry disease-causing genetic changes may be at significantly increased risk of developing leukemia cancer in their lifetime. For example, individuals with a pathogenic CEBPA mutation have ~90% lifetime risk to develop leukemia (Tawana, 2015). Frequently, changes in genes that result in increased risks for leukemia also predispose individuals to increased risks for other malignancies.

Included Disorders

This panel includes genes associated with:

  • Ataxia telangiectasia
  • Bloom syndrome
  • Choloangiocarcinoma
  • Constitutional mismatch repair syndrome
  • Costello syndrome
  • Dyskeratosis congenita
  • Familial acute myeloid leukemia
  • GATA2 deficiency
  • Li-Fraumeni syndrome
  • Neurofibromatosis type 1
  • Nijmegen breakage syndrome

Inheritance

Hereditary leukemia is typically inherited in an autosomal dominant manner, although several of the genes on this panel are associated with recessive genetic conditions:

  • MLH1, MSH2, PMS2, and MSH6 are associated with constitutional mismatch repair deficiency
  • ATM is associated with ataxia telangiectasia
  • BLM is associated with Bloom syndrome
  • TERT is associated with dyskeratosis congenita
  • NBN is associated with Nijmegen breakage syndrome

DKC1-related dyskeratosis congenita is inherited in an X-linked manner.

Indications for Testing

  • A personal history of early leukemia or myelodysplastic syndrome
  • A personal history of multiple primary cancers
  • A family history suggestive of a hereditary cancer syndrome, including multiple individuals on the same side of a family diagnosed with cancer, especially at ages below population averages
  • Risk assessment for asymptomatic family of members of proband with molecular diagnosis of a hereditary cancer syndrome

Methodology

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering.

Included Genes (18)

ATM BLM CEBPA DKC1 EPCAM GATA2 HRAS MLH1 MSH2
MSH6 NBN NF1 PMS2 RUNX1 TERC TERT TINF2 TP53

Additions to the Leukemia Panel:

Emerging evidence genes can also be added onto the comprehensive panel. These genes do not have a clear association with hereditary leukemia, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence (5):

BRCA1 BRCA2 BRIP1 CHEK2 PALB2

Fanconi Anemia Genes (17):

BRCA2 BRIP1 ERCC4 FANCA FANCB FANCC FANCD2 FANCE FANCF
FANCG FANCI FANCL FANCM PALB2 RAD51C SLX4 XRCC2

References:

  • Surveillance, Epidemiology, and End Results Program (SEERP). Cancer Stat Fact Sheets [Accessed April 20, 2017]. Available from: http://seer.cancer.gov/
  • Tawana K, Wang J, Renneville A, et al. Disease evolution and outcomes in familial AML with germline CEBPA mutations. Blood. 2015;126(10):1214-23.