Hereditary Pediatric Cancer Panel

SEQmethod-seq-icon Our Sequence Analysis is based on a proprietary targeted sequencing method OS-Seq™ and offers panels targeted for genes associated with certain phenotypes. A standard way to analyze NGS data for finding the genetic cause for Mendelian disorders. Results in 21 days. DEL/DUPmethod-dup-icon Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes. Results in 21 days. PLUSmethod-plus-icon Plus Analysis combines Sequence + Del/Dup (CNV) Analysis providing increased diagnostic yield in certain clinical conditions, where the underlying genetic defect may be detectable by either of the analysis methods. Results in 21 days.

Test code: ON0801

The Blueprint Genetics Hereditary Pediatric Cancer Panel analyzes 52 genes associated with inherited suscebtibility to pediatric cancer.

This Panel covers genes associated with a broad spectrum of hereditary cancer syndromes that may affect children. It has been estimated that around 1-10% of pediatric cancers are accounted for by these syndromes that have predominantly autosomal dominant inheritance pattern. The Hereditary Pediatric Cancer Panel is suited for detecting heritable germline mutations and may not be used for the detection of somatic mutations in tumor tissue. This Panel is part of the Comprehensive Hereditary Cancer Panel.

About Hereditary Pediatric Cancer

Childhood leukemia is the most common pediatric cancer and accounts for more than a third of all new cancer diagnoses in children and adolescents. Most cancers occurring in children are thought to be sporadic and a genetic predisposition is rarely evoked. However, a small proportion of childhood leukemia and solid tumors can be caused by known hereditary cancer syndromes. The hereditary cancers that occur commonly in children include retinoblastoma (RB1), Wilms tumor (WT1) and medulloblastoma (SUFU). The main forms of hereditary cancer syndromes affecting children, adolescents, and yound adults are Li-Fraumeni syndrome (TP53), hereditary pheochromocytoma-paraganglioma (SDH genes), pleuropulmonaryblastoma tumor predisposition syndrome (DICER1), rhabdoid tumor of the kidney (SMARCB1) and multiple endocrine neoplasia (MEN1 and RET). In particular, when children present with adult type cancers, such as skin or gastrointestinal tract cancer, underlying genetic predisposition should be suspected. The risk of developing cancer in individuals carrying pathogenic germline mutations varies but can be as high as 80% for SDH and 100% for RET mutation carriers. Genetic testing for pediatric cancer patients has important implications on screening, prevention and treatment.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more.

Genes in the Hereditary Pediatric Cancer Panel and their clinical significance
GeneAssociated phenotypesInheritanceClinVarHGMD
ALKNeuroblastomaAD1712
APCGardner syndrome, Desmoid disease, hereditary, Familial adenomatous polyposisAD2941780
AXIN2Oligodontia-colorectal cancer syndromeAD615
BAP1Tumor predisposition syndromeAD1373
BLMBloom syndromeAR5392
BMPR1A*Polyposis, juvenile intestinalAD38108
CDC73Carcinoma, parathyroid, Hyperparathyroidism, Hyperparathyroidism-jaw tumor syndromeAD2386
CDKN1CBeckwith-Wiedemann syndrome, IMAGE syndromeAD2579
CEBPAAcute myeloid leukemia, familialAD129
DICER1*DICER1 syndromeAD96109
DIS3L2*Perlman syndromeAR69
EPCAMDiarrhea 5, with tufting enteropathy, congenital, Colorectal cancer, hereditary nonpolyposisAD/AR1563
EZH2Weaver syndromeAD1436
FHHereditary leiomyomatosis and renal cell cancerAD89161
GATA2Myelodysplastic syndrome, Chronic neutropenia associated with monocytopenia, evolving to myelodysplasia and acute myeloid leukemia, Acute myeloid leukemia, Emberger syndrome, ImmunodeficiencyAD1976
GPC3Simpson-Golabi-Behmel syndromeXL2265
HRASCostello syndrome, Congenital myopathy with excess of muscle spindlesAD3026
MAXPheochromocytomaAD623
MEN1Hyperparathyroidism, familial primary, Multiple endocrine neoplasiaAD124699
MLH1Muir-Torre syndrome, Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR6701084
MSH2Muir-Torre syndrome, Endometrial cancer, Colorectal cancer, hereditary nonpolyposis,, Mismatch repair cancer syndromeAD/AR6461089
MSH6Endometrial cancer, Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR308426
NBNBreast cancer, Nijmegen breakage syndromeAD/AR5762
NF1*Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndromeAD2612607
NF2Schwannomatosis, NeurofibromatosisAD24423
NSD1Sotos syndrome, Weaver syndrome, Beckwith-Wiedemann syndromeAD212461
PHOX2BCentral hypoventilation syndrome, congenital, Neuroblastoma, susceptiblity to, Neuroblastoma with Hirschsprung diseaseAD570
PMS2*Mismatch repair cancer syndrome, Colorectal cancer, hereditary nonpolyposisAD/AR151266
PRF1Lymphoma, non-Hodgkin, Aplastic anemia, adult-onset, Hemophagocytic lymphohistiocytosisAR15165
PRKAR1AMyxoma, intracardiac, Acrodysostosis, Pigmented nodular adrenocortical disease, Carney complexAD50173
PTCH1Basal cell nevus syndromeAD46348
PTEN*Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos syndrome, Cowden syndromeAD192564
RB1RetinoblastomaAD1111013
RECQL4Baller-Gerold syndrome, RAPADILINO syndrome, Rothmund-Thomson syndromeAR3492
RETHirschsprung disease, Central hypoventilation syndrome, congenital, Pheochromocytoma, Medullary thyroid carcinoma, Multiple endocrine neoplasiaAD/AR80405
RUNX1Platelet disorder, familial, with associated myeloid malignancyAD1374
SDHA*Leigh syndrome/Mitochondrial respiratory chain complex II deficiency, Gastrointestinal stromal tumor, Paragangliomas, Dilated cardiomyopathy (DCM)AD/AR2339
SDHAF2ParagangliomasAD25
SDHBParaganglioma and gastric stromal sarcoma, Pheochromocytoma, Gastrointestinal stromal tumor, Paragangliomas, Cowden-like syndromeAD72249
SDHCParaganglioma and gastric stromal sarcoma, Gastrointestinal stromal tumor, ParagangliomasAD1453
SDHDParaganglioma and gastric stromal sarcoma, Pheochromocytoma, Paragangliomas, Carcinoid tumors, intestinal, Cowden syndromeAD42158
SMAD4Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasiaAD119128
SMARCB1Schwannomatosis, Rhabdoid tumor predisposition syndromeAD17115
STK11Peutz-Jeghers syndromeAD69399
SUFUMedulloblastoma, Basal cell nevus syndromeAD727
TMEM127PheochromocytomaAD2038
TP53Colorectal cancer, Li-Fraumeni syndrome, Ependymoma, intracranial, Choroid plexus papilloma, Breast cancer, familial, Adrenocortical carcinoma, Osteogenic sarcoma, Hepatoblastoma, Non-Hodgkin lymphomaAD148391
TSC1Lymphangioleiomyomatosis, Tuberous sclerosisAD61306
TSC2Lymphangioleiomyomatosis, Tuberous sclerosisAD141977
VHLErythrocytosis, familial, PheochromocytomaAD/AR143573
WRN*Werner syndromeAR2097
WT1Denys-Drash syndrome, Frasier syndrome, Wilms tumorAD23165
  • * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Blueprint Genetics offers a comprehensive hereditary pediatric cancer panel that covers classical genes associated with Beckwith-Wiedemann syndrome, Bloom syndrome, familial adenomatous polyposis, Gorlin syndrome, hereditary nonpolyposis colon cancer, hereditary paraganglioma-pheochromocytoma, hereditary retinoblastoma, juvenile polyposis syndrome, Li-Fraumeni syndrome, medulloblastoma predisposition, multiple endocrine neoplasia, nephroblastoma, neurofibromatosis type 1, neurofibromatosis type 2, pediatric cancer, Peutz-Jeghers syndrome, pleuropulmonary blastoma family tumor susceptibility syndrome, Rothmund-Thomson syndrome, Simpson-Golabi-Behmel syndrome, tuberous sclerosis complex, Von Hippel-Lindau disease and Werner syndrome. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

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ICD & CPT codes

CPT codes

SEQ81479
DEL/DUP81479

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.