Hematologic Malignancy Comprehensive Panel

  • Panel Description
  • Test Description
  • CPT Codes
  • Resources
  • Gene Descriptions

Panel Description

Leukemia
Lymphoma
Myelodysplastic syndrome
Bone Marrow Failure
The Hematologic Malignancy Comprehensive Panel examines 22 genes associated with bone marrow failure or cancers of the blood. These genes include those associated with specific syndromes, as well as those associated with familial susceptibility in the absence of other clinical findings.

Patients with a personal or family history suggestive of a hereditary hematologic malignancy, which could include progressive bone marrow failure, leukemia, lymphoma, myelodysplastic syndrome as well as physical findings or other health issues suggestive of a genetic syndrome. After consideration of a patient’s clinical and family history, this testing may be appropriate for some pediatric patients. (If there are specific genes that you do NOT want included, please indicate this on the test requisition form.) This test is designed to detect individuals with a germline pathogenic variant, and is not validated to detect mosaicism below the level of 20%. It should not be ordered on tumor tissue.

Patients identified with a hereditary susceptibility to hematologic cancer or bone marrow failure can benefit from increased surveillance and preventative steps to better manage their risks. Knowing the genetic cause of the hematologic abnormalities in an individual also reveals the inheritance pattern within a family. As a result, your patient’s family members can be tested to help define the risk to themselves and their families. Because preventative action and surveillance should begin in childhood for some genes included in this panel, testing of minors may be appropriate.

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
2 - 3 weeks
Call for details
ANKRD26, ATM, BLM, CEBPA, DDX41, EPCAM, GATA2, HRAS, IKZF1, MLH1, MSH2, MSH6, NBN, NF1, PAX5, PMS2, RUNX1, SAMD9L, SRP72, TERC, TERT, TP53 ( 22 genes )
99% at 50x
DNA extracted from cultured fibroblasts should be submitted instead of blood/saliva/buccal samples from individuals who have undergone allogeneic bone marrow transplant and from patients with hematologic malignancy.‚Äč
Test results and variant interpretation are based on the proper identification of the submitted specimen and use of correct human reference sequences at the queried loci. In very rare instances, errors may result due to mix-up or co-mingling of specimens. Positive results do not imply that there are no other contributions, genetic or otherwise, to the patient's phenotype, and negative results do not rule out a genetic cause for the indication for testing. Official gene names change over time. Fulgent uses the most up to date gene names based on HUGO Gene Nomenclature Committee (https://www.genenames.org) recommendations. If the gene name on report does not match that of ordered gene, please contact the laboratory and details can be provided. Result interpretation is based on the collected information and Alamut annotation available at the time of reporting. This assay is not designed or validated for the detection of mosaicism. DNA alterations in regulatory regions or deep intronic regions (greater than 20bp from an exon) will not be detected by this test. There are technical limitations on the ability of DNA sequencing to detect small insertions and deletions. Our laboratory uses a sensitive detection algorithm, however these types of alterations are not detected as reliably as single nucleotide variants. Rarely, due to systematic chemical, computational, or human error, DNA variants may be missed. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the confounding contribution of pseudogene sequences or other highly-homologous sequences, sometimes these may still interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Deletion/duplication analysis can identify alterations in genomic regions and is evaluated at a single exon resolution level in relevant genes associated with the patient's clinical presentation. For custom added genes and applicable genes that may be of interest, deletion/duplication analysis is evaluated at a resolution of two or more contiguous exons. When novel DNA duplications are identified, it is not possible to discern the genomic location or orientation of the duplicated segment, hence the effect of the duplication cannot be predicted. Where deletions are detected, it is not always possible to determine whether the predicted product will remain in-frame or not. Unless otherwise indicated, in regions that have been sequenced by Sanger, deletion/duplication analysis has not been performed. Patients with Bone Marrow Transplants: DNA extracted from cultured fibroblasts should be submitted instead of blood/saliva/buccal samples from individuals who have undergone allogeneic bone marrow transplant and from patients with hematologic malignancy.

Gene Notes
MSH2 Inversion of MSH2 exons 1-7 ("Boland" inversion) is assessed for Lynch Syndrome, Colorectal, Endometrial, and Prostate Cancer Panel testing (for both Focus and Comprehensive Panels) as well as Comprehensive Gastric Cancer Panel testing. Unless otherwise specified, this testing is not performed for other cancer panels, but is available upon request.
CPT Code 81450, 81479

NOTE:  The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.
WHY ORDER THIS TEST?

Resources

DescriptionDownload
Hereditary Hematologic Malignancy Genetic Testing Information for Patients
Genetic Testing for Hereditary Cancers Webinar

Gene Descriptions

Gene Reason Reference
ATM Biallelic pathogenic variants in ATM have been associated with ataxia-telangiectasia, which is associated with an increased risk for leukemia and lymphoma. PubMed: 20301790; OMIM: 607585, 208900
BLM Biallelic pathogenic variants in the BLM gene cause Bloom's syndrome. Individuals with Bloom's syndrome are at a greatly increased risk for many types of cancer, including leukemia and lymphoma. Cancers often occurring at younger than typical ages. Patients with Bloom's syndrome are hypersensitive to some forms of cancer treatment. Additionally, carriers of heterozygous pathogenic BLM variants may be at a small increased risk for breast cancer, as well as others (low/moderate penetrance). However, additional studies are needed to confirm an association. PubMed: 20301572, 19432957, 23404160, 24733792, 26358404; OMIM: 210900
RUNX1 Heterozygous pathogenic variants in the RUNX1 gene are associated with familial platelet disorder and an increased risk for myeloid malignancies. PubMed: 28179279, 18173751, 11830488
CEBPA Heterozygous pathogenic variants in the CEBPA gene are associated with an increased risk for myeloid malignancies. PubMed: 18173751, 10508512
GATA2 Autosomal dominant pathogenic variants in GATA2 are associated with GATA2 deficiency and Emberger syndromes, both of which increase an individual's risk for myelodysplasia and acute myeloid leukemia. PubMed: 24227816, 28179280; OMIM 137295, 614038
MSH6 Biallelic pathogenic variants in MSH6 have been associated with constitutional mismatch repair deficiency syndrome (CMMRD), which increases the risk for lymphoma and leukemia. At this time, carriers of heterozygous MSH6 pathogenic variants are not believed to have an increase for hematologic malignancy. PubMed: 20301390, 22692065; OMIM: 120438
HRAS Heterozygous pathogenic variants in HRAS cause Costello syndrome. There is some preliminary evidence that germline pathogenic HRAS variants may increase the risk for leukemia; however, additional studies are needed to confirm an association. PubMed: 20301680, 25742478; OMIM: 190020
EPCAM Autosomal dominant pathogenic variants in EPCAM cause Lynch syndrome. While Lynch syndrome has been associated with an increased risk for hematopoietic malignancies in some studies, additional research is needed to determine whether Lynch syndrome caused by variants in EPCAM influences susceptability. PubMed: 23730225, 20301390
MLH1 Biallelic pathogenic variants in MLH1 have been associated with constitutional mismatch repair deficiency syndrome (CMMRD), which increases the risk for lymphoma and leukemia. At this time, carriers of heterozygous MLH1 pathogenic variants are not believed to have an increase for hematologic malignancy. PubMed: 20301390, 22692065; OMIM: 120436
MSH2 Biallelic pathogenic variants in MSH2 have been associated with constitutional mismatch repair deficiency syndrome (CMMRD), which increases the risk for lymphoma and leukemia. At this time, carriers of heterozygous MSH2 pathogenic variants are not believed to have an increase for hematologic malignancy. PubMed: 20301390, 22692065; OMIM: 120437
NBN Heterozygous pathogenic variants in NBN (also known as NBS1) have been associated with a number of malignancies including melanoma, non-Hodkins lymphoma, medulloblastoma, and colorectal, prostate, and breast cancers . Other studies have shown possible associations with aplastic anemia and acute lymphoblastic leukemia. Biallelic pathogenic variants in NBN have been associated with Nijmegen Breakage syndrome (NBS). Individuals with NBS generally have progressive intellectual disability, growth restriction, and immunodeficiency; and are at an increased risk for a variety of cancers, including lymphoma, glioma, and medulloblastoma. PubMed: 14973119, 15185344, 16474176, 16770759, 18079974, 19908051, 21514219,15338273,11325820, 20301355; OMIM: 609135, 251260
NF1 Autosomal dominant pathogenic variants in NF1 cause Neurofibromatosis Type 1, which is associated with several types of benign tumors and cancer, including an increased risk for leukemia. PubMed: 17636453, 20301288, 9639526, 27787920; OMIM: 613113
PMS2 Biallelic pathogenic variants in PMS2 have been associated with constitutional mismatch repair deficiency syndrome (CMMRD), which increases the risk for lymphoma and leukemia. At this time, carriers of heterozygous PMS2 pathogenic variants are not believed to have an increase for hematologic malignancy. PubMed: 20301390, 22692065; OMIM: 120438
TERC Autosomal dominant pathogenic variants in TERC have been associated with dyskeratosis congenita, which is associated with an increased risk for bone marrow failure, myelodysplastic syndrome, and leukemia. PubMed: 20301779
TERT Both heterozygous and biallelic pathogenic variants in TERT have been associated with dyskeratosis congenita, which is associated with bone marrow failure, myelodysplastic syndrome, and leukemia. Patients with autosomal dominant (heterozygous) TERT pathogenic variants tend to have milder disease than those with the autosomal recessive (biallelic) form. PubMed: 20301780
TP53 Heterozygous pathogenic variants in the TP53 gene are associated with Li-Fraumeni syndrome, a condition that increases risk for many types of cancer. PubMed: 20301488, 26014290, 2614290; OMIM: 151623, 191170