Nervous System / Brain Cancer Comprehensive Panel

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

Panel Description

Brain Cancers
Nervous System Cancers
Neuroblastomas
Brain tumors
Pineoblastomas
Pituitary Blastomas
Familial Schwannomatosis
Multiple Endocrine Neoplasia
Ependymomas
Neurofibromatosis Types 1 and 2
Tuberous Sclerosis Complex
Neurofibromas
Peripheral Nerve Sheath Tumors
Schwannomas
Meningiomas
Astrocytomas
Medulloblastoma
Subependymal Nodules
Subependymal Giant Cell Astrocytomas
Brain Hemangioblastoma
The Nervous System/ Brain Cancer Comprehensive Panel examines 32 genes associated with an increased risk for nervous system or brain cancer. This test includes both well-established nervous system or brain cancer susceptibility genes, as well as candidate genes with limited evidence of an association.

Patients with a personal or family history suggestive of a hereditary nervous system or brain cancer syndrome. Red flags for hereditary cancer could include onset of cancer prior to the age of 50 years, more than one primary cancer in a single person, and multiple affected people within a family. The presence of more than one nervous system or brain cancers in first or second degree relatives, as well as the presence of other types of cancer, such as breast, colon, thyroid, ovarian, pancreatic, renal or prostate in a patient’s clinical or family history indicate that genetic testing for a hereditary nervous system or brain cancer syndrome may be warranted. After consideration of a patient’s clinical and family history, this testing may be appropriate for some pediatric patients as preventative steps may be warranted in childhood. (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 nervous system or brain cancer syndrome can benefit from increased surveillance and preventative steps to better manage their risk for cancer. Information obtained from candidate gene testing may potentially be helpful in guiding clinical management in the future. Also, if an inherited susceptibility is found, your patient’s family members can be tested to help define their risk. If a pathogenic variant is identified in your patient, close relatives (children, siblings, parents) could have as high as a 50% risk to also be at increased risk. In some cases, screening should begin in childhood.

Test Description

  • Sequencing
  • Del/Dup
  • Rush / STAT
  • Exclude VUS
2 - 3 weeks
Call for details
AIP, ALK, APC, ATM, CDKN1B, CDKN2A, DICER1, EPCAM, HRAS, KIF1B, LZTR1, MEN1, MLH1, MSH2, MSH6, NBN, NF1, NF2, PHOX2B, PMS2, POT1, PRKAR1A, PTCH1, PTEN, SMARCA4, SMARCB1, SMARCE1, SUFU, TP53, TSC1, TSC2, VHL ( 32 genes )
99% at 50x
Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)
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. 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 of genomic regions which are a single exon in size. 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 81445, 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 Brain Cancer Information for Patients
Genetic Testing for Hereditary Cancers Webinar

Gene Descriptions

Gene Reason Reference
ALK Autosomal dominant pathogenic variants in the ALK gene are associated with familial neuroblastoma, and confer a small increased risk (low penetrance) for this type of cancer. PubMed: 25124476, 28055978
APC Heterozygous pathogenic variants in APC are associated with both classic and attenuated familial adenomatous polyposis (FAP), Gardner syndrome, Turcot syndrome, and Hereditary Desmoid disease. PubMed: 20301519; OMIM: 175100
ATM Biallelic pathogenic variants in ATM have been associated with ataxia-telangiectasia, which may be associated with an increased risk for brain tumors. Additional research is needed. PubMed: 27911673, 20301790; OMIM: 607585, 208900
CDKN1B Pathogenic heterozygous variants in CDKN1B are associated with Multiple Endocrine Neoplasia, Type IV (MEN 4). PubMed: 20301710, 23652671, 26257968; OMIM: 610755
CDKN2A Heterozygous pathogenic CDKN2A variants are associated with an increased risk for hereditary melanoma and familial atypical multiple mole melanoma-pancreatic carcinoma (FAMMPC) syndrome. This includes a melanoma with risk for astrocytoma. PubMed: 28283772, 26337759, 21249757, 19260062; OMIM: 600160
MSH6 While heterozygous pathogenic variants in MSH6 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
HRAS Heterozygous pathogenic variants in HRAS cause Costello syndrome. Individuals with Costello syndrome have a 15% lifetime risk for developing a malignant tumor, which can include rhabdomyosarcoma, neuroblastoma, and carcinoma of the bladder. PubMed: 20301680, 27155140; OMIM: 190020
EPCAM Heterozygous pathogenic variants in the EPCAM gene cause Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, which increases the risk for brain cancer. Glioblastoma is the most common type, although other central nervous system tumors have been reported. PubMed: 20301390, 23462293
MEN1 Autosomal dominant pathogenic variants in the gene MEN1 cause Multiple endocrine neoplasia type 1 (MEN1), which is associated with an increased risk for both endocrine and non-endocrine tumors, including meningiomas and ependymomas. PubMed: 20301710; OMIM: 131100
MLH1 While heterozygous pathogenic variants in MLH1 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
MSH2 While heterozygous pathogenic variants in MSH2 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
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 neurofibromas, optic glioma, plexiform neurofibromas. PubMed: 17636453, 20301288, 9639526, 27787920; OMIM: 613113
NF2 Heterozygous pathogenic variants in NF2 are associated with Neurofibromatosis, Type 2. Individuals with this condition are at an increased risk for bilateral vestibular schwannomas, as well as other types of tumors. PubMed: 20301380; OMIM: 607379
PMS2 While heterozygous pathogenic variants in PMS2 are associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, biallelic pathogenic variants have been associated with constitutional mismatch repair deficiency syndrome (CMMRD). PubMed: 20301390, 22692065; OMIM: 120436
PRKAR1A Heterozygous pathogenic variants in PRKAR1A are associated with Carney Complex. Individuals with this condition are at approximately a 10% risk to develop a schwannoma, in addition to other clinical findings. PubMed: 20301463; OMIM: 188830
PTCH1 Autosomal dominant pathogenic variants in PTCH1 are associated with Nevoid Basal Cell Carcinoma syndrome (NBCSS), which increases the risk for medulloblastoma. For individuals with NBCSS caused by PTCH1 variants, this risk, though, is less than 2%. PubMed: 20301330; OMIM: 601309
PTEN Autosomal dominant pathogenic variants in PTEN have been associated with Cowden syndrome, which is associated with an increased risk for brain tumors. Additional research is needed to further define this relationship. PubMed: 20301661; OMIM: 601728
SMARCA4 Autosomal dominant pathogenic variants in SMARCA4 are associated with an increased risk for schwannomas and with Rhabdoid Tumor Predisposition Syndrome (RTPS). This condition is associated with an increased risk for rhabdoid tumors, such as small cell carcinoma of the ovary, hypercalcemic type and rhabdoid tumors of the kidney, as well as others. PubMed: 25494491, 24752781, 24658002
SMARCB1 Heterozygous pathogenic variants in SMARCB1 are associated with familial schwannomatosis and familial rhabdoid tumor predisposition syndrome. SMARCB1 germline pathogenic variants are responsible for approximately 45% of cases of familial schwannomatosis. PubMed: 26941181; OMIM: 609322
SMARCE1 There is some evidence that heterozygous pathogenic germline variants in SMARCE1 are associated with risk for meningioma. Additional research is needed to confirm this association given the small number of reported cases to date. PubMed: 25249420, 26803492
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
TSC1 Autosomal dominant pathogenic variants in TSC1 cause Tuberous Sclerosis complex, which is associated with several types of brain tumors, including subependymal nodules and subependymal giant cell astrocytomas. PubMed: 20301399; OMIM: 605284
TSC2 Autosomal dominant pathogenic variants in TSC2 cause Tuberous Sclerosis complex, which is associated with several types of tumors, including subependymal nodules and subependymal giant cell astrocytomas PubMed: 20301399; OMIM: 191092
VHL Heterozygous pathogenic variants in VHL cause von Hippel-Lindau (VHL) syndrome, which increases the risk for many types of cancer, including hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma, and neuroendocrine tumors. The most common location for the development of a hemangioblastoma is in the brain, but spinal cord hemangioblastomas as also common in VHL. PubMed: 20301636, 27114602, 25834951, 24355456
LZTR1 Autosomal dominant pathogenic variants in LZTR1 are associated with an increased risk for schwannomatosis. PubMed: 24362817, 27921248, 2829512; OMIM: 615670)
PHOX2B Autosomal dominant pathogenic variants in the PHOX2B gene are associated with familial neuroblastoma. PubMed: 25124476, 28055978
DICER1 Autosomal dominant mutations in DICER1 have been associated with DICER1 syndrome, a familial tumor susceptibility syndrome which includes susceptibility to many different kinds of tumors. PubMed: 24761742; OMIM: 606241
SUFU Autosomal dominant pathogenic variants in SUFU have been associated with Nevoid basal cell Carcinoma syndrome (NBCCS; also called Gorlin syndrome). Individuals with NBCCS have up to a 33% risk for developing medulloblastoma, and also have ain increased risk to develop post-radiation meningioma. PubMed: 20301330; OMIM: 607035
POT1 Autosomal dominant pathogenic variants in POT1 has been associated with an increased risk for melanoma and gliomas PubMed: 26337759, 28283772, 25482530, 24686846, 27528712, 24686849; OMIM: 606478