Invitae Pediatric Solid Tumors Panel

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  • Test code: 01104
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

This test analyzes 48 genes that are associated with a hereditary predisposition to the development of pediatric solid tumors. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive panel for pediatric solid tumors. Some of these genes are also associated with an increased risk of other cancer types.

Recent studies of cohorts of pediatric cancer patients have reported predisposing pathogenic genetic variants for several childhood cancers. The results show that approximately 10% of children who develop cancer have an underlying cancer-predisposing condition. Genetic testing of these genes may confirm a diagnosis and can substantially influence the choice of appropriate screening and medical management options for the child and other relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (48 genes)

ALK APC AXIN2 BAP1 BLM BMPR1A CDC73 CDKN1C DICER1 DIS3L2 EPCAM FH GPC3 HRAS MAX MEN1 MLH1 MSH2 MSH6 NBN NF1 NF2 PHOX2B PMS2 PRKAR1A PTCH1 PTEN RB1 RECQL4 RET SDHA SDHAF2 SDHB SDHC SDHD SMAD4 SMARCA4 SMARCB1 SMARCE1 STK11 SUFU TMEM127 TP53 TSC1 TSC2 VHL WRN WT1

Advances in genetic testing and studies of cohorts of pediatric cancer patients have reported predisposing gene mutations for several childhood cancers. Identification of a hereditary cancer predisposition in childhood or adolescence can substantially influence the choice of appropriate screening and medical management options for the child and other relatives.

Solid tumors comprise approximately 30% of all pediatric cancers. Pediatric solid tumors include carcinomas and sarcomas that can develop nearly anywhere in the body. The most common types include brain tumors, neuroblastoma, rhabdomyosarcoma, Wilms tumor, and osteosarcoma.

Recent studies suggest that approximately 10% of all pediatric cancers are due to an underlying germline pathogenic variant. Zhang et al., 2015 identified pathogenic variants in cancer-related genes among a significant proportion of individuals with pediatric solid tumors (16.7% of those with non-central nervous system solid tumors and 8.6% of those with central nervous system solid tumors). This suggests utility in evaluating this population for hereditary cancer conditions as results may allow for condition-specific medical management and surveillance, provide recurrence risk assessment, and guide family planning.

Individuals with a pathogenic variant in one of these genes have an increased risk of malignancy compared to the average person, but not everyone with such a variant will actually develop cancer. Further, the same variant can present differently, even among individuals within the same family.

Major tumor subtypes included in this test

Tumor type Genes
Colorectal AXIN2, APC, BLM, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, PTEN, SMAD4, STK11, TP53
Meningioma NF2, SMARCE1, MEN1, WRN
Neuroblastoma ALK, HRAS, PHOX2B
Nevus basal cell carcinoma and medulloblastoma PTCH1, SUFU
Paraganglioma/ Pheochromocytoma (PGL/PCC) MAX, NF1, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL
Renal (including Wilms tumor) BAP1, CDC73, CDKN1C, DIS3L2, FH, GPC3, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TSC1, TSC2, VHL, WT1
Rhabdoid tumor and small-cell carcinoma of the ovary, hypercalcemic type SMARCB1, SMARCA4
Rhabdomyosarcoma and (other sarcomas) DICER1, EPCAM, MLH1, MSH2, MSH6, PMS2, HRAS, NBN, (APC, BLM, FH, RB1, RECQL4, TP53, WRN

Conditions and tumor types by gene

Gene Condition Tumor types PMIDs/references
ALK Familial neuroblastoma neuroblastoma 18724359, 18923523, 22071890, 18923503
APC Familial adenomatous polyposis (FAP) colon, thyroid, hepatoblastoma, sarcoma 8150351, 18063416, 19822006, 1673441, 3036290, 7698732
AXIN2 Oligodontia-colorectal cancer syndrome colorectal 21416598, 26025668, 15042511
BAP1 BAP1 hereditary cancer predisposition syndrome renal cell carcinoma, uveal melanoma, mesothelioma 26096145
BLM Bloom syndrome connective tissue carcinoma, sarcoma Bloom’s syndrome registry: http://weill.cornell.edu/bsr/data_from_registry/
BMPR1A Juvenile polyposis syndrome colorectal, gastric, pancreatic, juvenile GI polyps 25645574, 16246179, 17303595, 20859198, 9869523
CDC73 CDC73-related conditions parathyroid carcinoma, ossifying jaw fibromas, benign renal tumors 20301744, 15606373
CDKN1C Beckwith-Wiedemann syndrome Wilms tumor, hepatoblastoma, rhabdomyosarcoma 16010495, 12138139
DICER1 DICER1 syndrome pleuropulmonary blastoma and cystic nephroma, rhabdomyosarcoma, pituitary blastoma, pineoblastoma 24839956, 22180160, 21266384
DIS3L2 Perlman syndrome Wilms tumor 18780370, 23613427, 22306653
EPCAM Constitutional mismatch repair deficiency (CMMR-D) brain and nervous system, colorectal, rhabdomyosarcoma 24440087, 24737826, 24556086
FH hereditary leiomyomatosis, renal cell cancer (HLRCC); autosomal recessive fumarase deficiency renal cell carcinoma, uterine leiomyosarcoma 25012257, 20301430, 25018647, 16477632
GPC3 Simpson-Golabi-Behmel syndrome Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma 16010678, 16010678, 25238977, 23606591, 20301398
HRAS Costello syndrome rhabdomyosarcoma, neuroblastoma 11857556, 20301680, 22261753
MAX Hereditary paraganglioma-pheochromocytoma syndrome (PGL/PCC) paraganglioma, pheochromocytoma 24523625, 26347711, 22452945
MEN1 Multiple endocrine neoplasia type 1 (MEN1) parathyroid adenoma, anterior pituitary, thyroid (including goiter), adrenocortical carcinoma, meningioma 23933118, 11836268, 22084155, 19904212
MLH1 Constitutional mismatch repair deficiency (CMMR-D) brain and nervous system, colorectal, rhabdomyosarcoma 24440087, 24737826, 24556086
MSH2 Constitutional mismatch repair deficiency (CMMR-D) brain and nervous system, colorectal, rhabdomyosarcoma 24440087, 24737826, 24556086
MSH6 Constitutional mismatch repair deficiency (CMMR-D) brain and nervous system, colorectal, rhabdomyosarcoma 24440087, 24737826, 24556086
NBN Nijmegen breakage syndrome (NBS) medulloblastomas, gliomas, rhabdomyosarcomas 15474156
NF1 Neurofibromatosis type 1 (NF1) schwannoma, pheochromocytoma, optic glioma, neurofibromas 25130111, 20833335, 24535705
NF2 Neurofibromatosis type 2 (NF2) vestibular schwannoma, spinal schwannoma, meningioma 19652604, 21278391, 15945431, 19652604
PHOXB2 Familial neuroblastoma neuroblastoma 25124476, 25435121
PMS2 Constitutional mismatch repair deficiency (CMMR-D) brain and nervous system, colorectal, rhabdomyosarcoma 24440087, 24737826, 24556086
PRKAR1A Carney complex nerve sheath, thyroid, sarcoma, large-cell calcifying Sertoli cell 26130139, 16756677, 20301463
PTCH1 Basal cell nevus syndrome (Gorlin syndrome) basal cell carcinoma, medulloblastoma 26409035, 20301330
PTEN PTEN hamartoma syndrome thyroid, colon 22252256
RB1 Familial retinoblastoma retinoblastoma, sarcoma, melanoma 22355046, 20301625, 8304343
RECQL4 Rothmund-Thomson syndrome, Baller-Gerold syndrome, RAPADILINO syndrome osteosarcoma, basal cell carcinoma, squamous cell carcinoma 11471165, 12952869
RET Multiple endocrine neoplasia type 2 medullary thyroid carcinoma, pheochromocytoma 20301434, 21862994
SDHA Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal 23612575, 17804857, 24096523, 26113606, 20301715, 24523625
SDHAF2 Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal, renal, thyroid 20301715, 24523625
SDHB Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal, renal, thyroid 17667967, 17804857, 24096523, 26113606, 26347711, 20301715, 24523625
SDHC Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal, renal, thyroid 17667967, 17804857, 21173220, 24903423, 20301715, 24523625
SDHD Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal, renal, thyroid 17667967, 17804857, 16317055, 20301715, 24523625
SMARCA4 small-cell carcinoma of the ovary, hypercalcemic type 26975901, 27100627
SMAD4 Juvenile polyposis syndrome colorectal, gastric, pancreatic, juvenile GI polyps 20301642, 25645574, 17303595, 16246179, 9869523
SMARCB1 Rhabdoid tumor predisposition syndrome rhabdoid, schwannomas 22434719, 24933152, 21208904, 17357086
SMARCE1 clear cell meningioma 25249420, 25143307
STK11 Peutz-Jeghers syndrome colorectal, gastric, pancreatic, duodenal, lung 20051941, 20581245, 25645574
SUFU Basal cell nevus syndrome (Gorlin syndrome) basal cell carcinoma, medulloblastoma 22508808, 19833601, 12068298, 20301330, 25403219
TMEM127 Hereditary PGL/PCC paraganglioma, pheochromocytoma, gastrointestinal stromal, renal, thyroid 24899893, 26347711
TP53 Li-Fraumeni syndrome adrenocortical carcinoma, choroid plexus carcinoma, sarcomas, brain/nervous system, colorectal, many others 10864200, 20522432, 20301488
TSC1 Tuberous sclerosis brain/nervous system, renal 21182496, 9568761
TSC2 Tuberous sclerosis brain and nervous system, renal 21182496, 9568761
VHL von Hippel Lindau syndrome hemangioblastoma, renal cell carcinoma, pancreatic neuroendocrine (PNET), pheochromocytoma, epididymal 21386872, 25611110, 21955200, 26279462, 24899893
WRN Werner syndrome soft-tissue sarcoma, osteosarcoma, melanoma, thyroid carcinoma, meningioma 20301687, 23573208, 14676353
WT1 WT1-related disorders (Denys-Drash, WAGR, Frasier syndrome) Wilms tumor 12193442, 25688735, 8827067, 25623218, 20301471, 15150775

Most of the genes on this panel confer an increased risk of developing pediatric solid tumors in an autosomal dominant inheritance pattern. EPCAM, MLH1, MSH2, MSH6, and PMS2 are associated with autosomal recessive constitutional mismatch repair deficiency (CMMR-D), FH is associated with autosomal recessive fumarase deficiency, GPC3 is associated with X-linked Simpson-Golabi-Behmel syndrome, and SDHA is associated with autosomal recessive mitochondrial complex II deficiency syndrome.

Carriers (heterozygotes) of any of the above autosomal recessive conditions have an increased risk for adult-onset cancers. This information will be included in the test report when a result is present.

This panel may be considered for children or young adults with the types of solid tumors listed above. Other candidates for testing include those whose clinical or family history is suggestive of a hereditary cancer syndrome.

There are also some common, general features suggestive of a hereditary cancer syndrome family. These include:

  • cancer diagnosed at an unusually young age
  • different types of cancer that have occurred independently in the same person
  • cancer that has developed in both of a set of paired organs (e.g., both kidneys, both breasts)
  • several close blood relatives that have the same type of cancer
  • unusual cases of a specific cancer type (e.g., breast cancer in a man)

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  7. Clarke, BA, et al. Loss of SMARCA4 (BRG1) Protein Expression by Immunohistochemistry in Small Cell Carcinoma of the Ovary, Hypercalcemic Type Distinguishes these Tumors from their Mimics. Histopathology. 2016. PMID: 27100627
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Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALK NM_004304.4
APC* NM_000038.5
AXIN2 NM_004655.3
BAP1 NM_004656.3
BLM NM_000057.3
BMPR1A* NM_004329.2
CDC73 NM_024529.4
CDKN1C NM_000076.2
DICER1 NM_177438.2
DIS3L2 NM_152383.4
EPCAM* NM_002354.2
FH NM_000143.3
GPC3 NM_004484.3
HRAS NM_005343.2
MAX NM_002382.4
MEN1 NM_130799.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
NBN NM_002485.4
NF1 NM_000267.3
NF2 NM_000268.3
PHOX2B* NM_003924.3
PMS2 NM_000535.5
PRKAR1A NM_002734.4
PTCH1 NM_000264.3
PTEN* NM_000314.4
RB1 NM_000321.2
RECQL4 NM_004260.3
RET NM_020975.4
SDHA* NM_004168.3
SDHAF2 NM_017841.2
SDHB NM_003000.2
SDHC NM_003001.3
SDHD NM_003002.3
SMAD4 NM_005359.5
SMARCA4 NM_001128849.1
SMARCB1 NM_003073.3
SMARCE1 NM_003079.4
STK11 NM_000455.4
SUFU NM_016169.3
TMEM127 NM_017849.3
TP53* NM_000546.5
TSC1 NM_000368.4
TSC2 NM_000548.3
VHL NM_000551.3
WRN* NM_000553.4
WT1 NM_024426.4

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.
BMPR1A: Deletion/duplication analysis covers the promoter region.
EPCAM: Analysis is limited to deletion/duplication analysis
MLH1: Deletion/duplication analysis covers the promoter region.
MSH2: Analysis includes the exon 1-7 inversion (Boland mutation).
PHOX2B: Alanine repeat numbers for the commonly expanded region in exon 3 are not determined.
PTEN: Deletion/duplication analysis covers the promoter region.
SDHA: Analysis is limited to sequencing analysis. No clinically-relevant del/dups have been reported.
TP53: Deletion/duplication analysis covers the promoter region.
WRN: Deletion/duplication analysis is not offered for exons 10 or 11.