CLINICAL CAPABILITIES // Genetic testing

Paraganglioma-Pheochromocytoma

Identify genetic risk factors and causes of rare cancer.

Clinical at Psomagen

Who Would Benefit from Paraganglioma-Pheochromocytoma Genetic Testing?

1

A person with a strong family history of certain types of cancer

Determine if they carry a gene mutation that increases their risk. If they do have an inherited mutation, they might want to have screening tests to look for cancer early, or even take steps to try to lower their risk.

2

A person already diagnosed with cancer

This is especially true if there are other factors to suggest the cancer might have been caused by an inherited mutation (such as a strong family history or if the cancer was diagnosed at a young age). Genetic testing might show if the person has a higher risk of developing cancer. It can also help other family members decide if they want to be tested for the mutation.  

3

Family members of a person known to have an inherited gene mutation that increases their risk of cancer

Testing can help them know if they need screening tests to look for cancer early, or if they should take steps to try to lower their risk.

How Do I Order a Test?

A printed copy of the requisition form must be submitted with the specimen if you are not placing your order through the online portal. You can find and print a copy of the requisition form here. If you need to modify your order, please contact client services.

Paraganglioma-Pheochromocytoma Panel Best Practices

Preferred Specimen

2mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)

Alternate Specimens

  • Saliva
  • Buccal swab
  • gDNA
Let's get started!

How to Ship Your Samples

Follow IATA Regulations

Please note that Psomagen sample collection kits are built to protect the samples from being damaged during transport and to comply with the International Air Transport Association (IATA) regulation. If you are using packaging other than that provided by Psomagen, please make sure to follow the "three layers of packaging" rule to avoid the risk of having the package destroyed by the courier:

  • A primary sample receptacle sealed (collection tube).
  • A leak-proof specimen bag containing absorbent material.
  • An outer packaging that meets the local postal regulations and is labeled as “Exempt Human Specimen.”

For more information please refer to page 187 of IATA Dangerous Goods Regulation.

Additional Shipment Requirements

For saliva, ship at room temperature (overnight shipping is not necessary).

For blood, we recommend using overnight shipping the same day that the blood is collected.

  • Blood can be kept at room temperature for up to 48 hours.
  • We request that blood is refrigerated no longer than two weeks.
  • Please do not freeze blood as deletion/duplication analysis is not supported for frozen or partially frozen blood.

Please ship the specimen in a crush-proof container via FedEx Priority Overnight (in accordance with the FedEx Packaging Guidelines for Clinical Samples.

Our US Shipping Address

Attn: Clinical Laboratory Testing Personnel
Psomagen Inc.
1330 Piccard Drive, Ste 103
Rockville, MD 20850

Test for 11 related genes

Gene List

FH
MAX
NF1
RET
SDHA
SDHAF2
SDHB
SDHC
SDHD
TMEM127
VHL
 

Test Methodology and Limitations

DNA sequencing involves the extraction of genomic DNA from specimens collected in approved containers and provided the specimen meets required sample minimum quantity (e.g. volume, weight, etc). This is followed by quantification and qualification to ensure the adequacy of amount and purity for sequencing. Subsequently, whole exome sequencing is conducted on an IlluminaTM short read sequencing (SRS) platform (e.g., Novaseq X PlusTM) at Psomagen, Inc.’s laboratories (CLIA # 21D2062464, CAP # 8742212).

DNA sequence alignment, variant calling, and variant filtering are performed utilizing the Illumina DRAGENTM bioinformatics pipeline (version 4.2.4.) and various tool sets, which align reads to the human reference genome (GRCh38) and identify single nucleotide variants (SNVs) and small insertions/deletions (InDels). Variant annotations are performed using a pipeline available in Fabric Enterprise. Variant review and interpretation are conducted according to the standards and guidelines set forth by the American College of Medical Genetics and Genomics (Richards S, et al., Genet Med., 2015) by Fabric Clinical Labs (CLIA #45D2281059, CAP # 9619501). Only variants classified as pathogenic or likely pathogenic are reported. The following quality filters are applied to all variants: coverage <40x, allele balance outside 0.3-0.7.

Variants in the following genes are reported: FH, MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL.

This test is designed to detect single nucleotide variants (SNVs) and small insertions/deletions (InDels). Next-Generation Sequencing (NGS) coverage may vary across the genome, potentially resulting in missed variants in regions with low coverage depth. Some genetic abnormalities may be undetectable with the current version of this test. While the DRAGEN bioinformatics pipeline demonstrates high accuracy for variant calling, there remains a possibility of false positive or false negative results due to variant interpretation which relies on current scientific knowledge and available databases. This may lead to the reclassification of reported variants as new information emerges from ongoing research and is updated in the ACMG guidelines. Furthermore, systematic chemical, computational, or human errors may contribute to false positives or false negatives of DNA variants. For any reported variants, confirmation by orthogonal technology and subsequent consultation with a genetic counselor or qualified healthcare provider can help to establish definitive risk. This result should be considered preliminary until such confirmation has been performed.

Clinical management for this individual should be based on personal and family history, along with other relevant information. If considered relevant to this individual’s clinical presentation and/or family history, targeted testing of appropriate family members of this individual for the reported variants may help to interpret these results. For assistance with the interpretation of these results, healthcare professionals may contact Psomagen directly at (301) 251-1007 or support@psomagen.com.

More Resources

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  3. Welander J, Soderkvist P, Gimm O. Genetics and clinicalcharacteristics of hereditary pheochromocytomas and para-gangliomas. Endocr Relat Cancer 2011; 18: R253–76.

  4. Benn DE, Robinson BG, Clifton-Bligh RJ. 15 Years ofparaganglioma: clinical manifestations of paragangliomasyndromes types 1-5. Endocr Relat Cancer 2015; 22: T91–103.

  5. Crona J, Taieb D, Pacak K. New perspectives on pheochro-mocytoma and paraganglioma: toward a molecular classifi-cation. Endocr Rev 2017; 38: 489–515.

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  7. Sutton MG, Sheps SG, Lie JT. Prevalence of clinicallyunsuspected pheochromocytoma. Review of a 50-yearautopsy series. Mayo Clin Proc 1981; 56: 354–60.

  8. Welander J, Andreasson A, Juhlin CC et al. Rare germlinemutations identified by targeted next-generation sequencingof susceptibility genes in pheochromocytoma and paragan-glioma. J Clin Endocrinol Metab 2014; 99: E1352–60.

  9. Fishbein L, Leshchiner I, Walter V et al. Comprehensivemolecular characterization of pheochromocytoma and para-ganglioma. Cancer Cell 2017; 31: 181–93.

  10. Badenhop RF, Cherian S, Lord RS, Baysal BE, Taschner PE,Schofield PR. Novel mutations in the SDHD gene in pedi-grees with familial carotid body paraganglioma and sen-sorineural hearing loss. Genes Chromosom Cancer 2001; 31:255–63.

  11. Hao HX, Khalimonchuk O, Schraders M et al. SDH5, a generequired for flavination of succinate dehydrogenase, ismutated in paraganglioma. Science 2009; 325: 1139–42.

  12. Castro-Vega LJ, Buffet A, De Cubas AA et al. Germlinemutations in FH confer predisposition to malignantpheochromocytomas and paragangliomas. Hum Mol Genet2014; 23: 2440–6.

  13. Dackiw AP, Cote GJ, Fleming JB et al. Screening for MEN1mutations in patients with atypical endocrine neoplasia.Surgery 1999; 126: 1097–103.

  14. Xu W, Mulligan LM, Ponder MA et al. Loss of NF1 alleles inphaeochromocytomas from patients with type I neurofibro-matosis. Genes Chromosom Cancer 1992; 4: 337–42