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  • Test code: 01722
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top EDTA tube (K2EDTA or K3EDTA)
  • Alternate specimens:
    Saliva, assisted saliva, buccal swab and gDNA
  • Sample requirements
  • Request a sample kit
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  1. Test Catalog
  2. Invitae Basal Cell Nevus Syndrome Panel

Invitae Basal Cell Nevus Syndrome Panel

Test description

This test analyzes the PTCH1 and SUFU genes, which are associated with basal cell nevus syndrome (BCNS). BCNS, also known as Gorlin syndrome, is a multisystemic neurocutaneous condition that increases the risk of developing various tumors—most notably, basal cell carcinomas and keratocystic odontogenic tumors. Other features include bifid ribs, palmar pits, and macrocephaly.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Genes tested

Primary panel

PTCH1 SUFU

Add-on Preliminary-evidence Gene for Basal Cell Nevus Syndrome

PTCH2

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

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Primary panel (2 genes)

PTCH1 SUFU

Panel details and technical assay limitations
Add-on Preliminary-evidence Gene for Basal Cell Nevus Syndrome (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

PTCH2

Panel details and technical assay limitations

Clinical information

  • basal cell nevus syndrome (BCNS) – also known as Gorlin syndrome

Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, is characterized by the early development of numerous basal cell carcinomas. Other associated tumor types include benign cutaneous cysts, cardiac and ovarian fibromas, and medulloblastomas. Additional features include benign jaw cysts, palmar pits, calcification of the cranial sutures, bridged sella turcica, clefting, polydactyly, and bifid ribs. Affected individuals may also present with macrocephaly, hypertelorism, and frontal bossing. BCNS has a variable clinical presentation: Not all affected individuals will present with all of these symptoms.

Individuals with BCNS have a 90% risk of developing multiple basal cell skin cancers. Approximately 5% of affected children will develop medulloblastoma, a type of brainstem tumor. Individuals with pathogenic SUFU variants have been reported to have a substantially higher risk of developing medulloblastoma (~30%) compared to those with a PTCH1 pathogenic variant (<2%). The risk of other malignant tumors is currently unclear. BCNS is highly variable, meaning individuals with BCNS may present differently, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may benefit most patients who are found to have a pathogenic variant.

Pathogenic variants in PTCH1 and SUFU account for an estimated 70% and 6% of clinically diagnosed cases of BCNS, respectively.

Approximately 70%–80% of BCNS cases are inherited from an affected parent in an autosomal dominant pattern. The remainder are sporadic and occur as the result of a spontaneous de novo mutation.

The prevalence of BCNS is estimated at 1 in 18,000 to 1 in 30,000 individuals.

Testing for BCNS may be considered in individuals with the following:

  • lamellar (sheet-like) calcification of the falx
  • jaw keratocyst(s)
  • palmar/plantar pits (two or more)
  • multiple basal cell carcinomas
  • first-degree relative with NBCCS
  • childhood medulloblastoma
  • macrocephaly (occipital frontal circumference >97th centile)
  • cleft lip/palate
  • vertebral/rib anomalies
  • preaxial or postaxial polydactyly
  • ovarian/cardiac fibromas
  • ocular anomalies

  1. Evans, DG, Farndon, PA. Nevoid Basal Cell Carcinoma Syndrome. 2002 Jun 20. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1151/ PMID: 20301330
  2. Kimonis, VE, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am. J. Med. Genet. 1997; 69(3):299-308. doi: 10.1002/(sici)1096-8628(19970331)69:3<299::aid-ajmg16>3.0.co;2-m. PMID: 9096761
  3. Bree, AF, et al. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am. J. Med. Genet. A. 2011; 155A(9):2091-7. doi: 10.1002/ajmg.a.34128. PMID: 21834049
  4. Boutet, N, et al. Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. J. Invest. Dermatol. 2003; 121(3):478-81. doi: 10.1046/j.1523-1747.2003.12423.x. PMID: 12925203
  5. Evans, DG, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J. Med. Genet. 1993; 30(6):460-4. doi: 10.1136/jmg.30.6.460. PMID: 8326488
  6. Evans, DG, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am. J. Med. Genet. A. 2010; 152A(2):327-32. doi: 10.1002/ajmg.a.33139. PMID: 20082463
  7. Brugières, L, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J. Clin. Oncol. 2012; 30(17):2087-93. PMID: 22508808
  8. Cowan, R, et al. The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br. J. Cancer. 1997; 76(2):141-5. doi: 10.1038/bjc.1997.354. PMID: 9231911
  9. Fujii, K, Miyashita, T. Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review. Pediatr Int. 2014; 56(5):667-74. doi: 10.1111/ped.12461. PMID: 25131638
  10. Jones EA, et al. Basal cell carcinomas in gorlin syndrome: a review of 202 patients. J Skin Cancer. 2011;2011:217378. PMID: 21152126
  11. Kool M, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014 Mar 17;25(3):393-405. PMID: 24651015
  12. Pastorino L, et al. Identification of a SUFU germline mutation in a family with Gorlin syndrome. Am J Med Genet A. 2009 Jul;149A(7):1539-43. PMID: 19533801
  13. Kijima C, et al. Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation. Fam Cancer. 2012 Dec;11(4):565-70. PMID: 22829011
  14. Smith, MJ, et al. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J. Clin. Oncol. 2014; 32(36):4155-61. PMID: 25403219
  15. Lo, Muzio, L, et al. Clinical utility gene card for: Gorlin syndrome--update 2013. Eur. J. Hum. Genet. 2013; 21(10):None. doi: 10.1038/ejhg.2012.299. PMID: 23361221

Diagnostic criteria and surveillance recommendations have been proposed at the first international colloquium on BCNS in 2011:

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 and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PTCH1 NM_000264.3
PTCH2 NM_003738.4
SUFU NM_016169.3

Clinical resources
Dermatology gene list Genes and associated cancers chart Hereditary cancer gene list Hereditary cancer risks and references chart Invitae brochure
Patient resources
Patient guide: Genetic testing for hereditary cancer Patient guide: Genetic testing simplified Patient guide: Hereditary breast cancer Patient guide: Hereditary colorectal cancer
Test information
Forms page Specimen requirements page

References

  1. Boutet, N, et al. Spectrum of PTCH1 mutations in French patients with Gorlin syndrome. J. Invest. Dermatol. 2003; 121(3):478-81. doi: 10.1046/j.1523-1747.2003.12423.x. PMID: 12925203
  2. Bree, AF, et al. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am. J. Med. Genet. A. 2011; 155A(9):2091-7. doi: 10.1002/ajmg.a.34128. PMID: 21834049
  3. Brugières, L, et al. High frequency of germline SUFU mutations in children with desmoplastic/nodular medulloblastoma younger than 3 years of age. J. Clin. Oncol. 2012; 30(17):2087-93. PMID: 22508808
  4. Cowan, R, et al. The gene for the naevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br. J. Cancer. 1997; 76(2):141-5. doi: 10.1038/bjc.1997.354. PMID: 9231911
  5. Evans, DG, Farndon, PA. Nevoid Basal Cell Carcinoma Syndrome. 2002 Jun 20. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1151/ PMID: 20301330
  6. Evans, DG, et al. Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am. J. Med. Genet. A. 2010; 152A(2):327-32. doi: 10.1002/ajmg.a.33139. PMID: 20082463
  7. Evans, DG, et al. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. J. Med. Genet. 1993; 30(6):460-4. doi: 10.1136/jmg.30.6.460. PMID: 8326488
  8. Fujii, K, Miyashita, T. Gorlin syndrome (nevoid basal cell carcinoma syndrome): update and literature review. Pediatr Int. 2014; 56(5):667-74. doi: 10.1111/ped.12461. PMID: 25131638
  9. Jones EA, et al. Basal cell carcinomas in gorlin syndrome: a review of 202 patients. J Skin Cancer. 2011;2011:217378. PMID: 21152126
  10. Kijima C, et al. Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation. Fam Cancer. 2012 Dec;11(4):565-70. PMID: 22829011
  11. Kimonis, VE, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am. J. Med. Genet. 1997; 69(3):299-308. doi: 10.1002/(sici)1096-8628(19970331)69:3<299::aid-ajmg16>3.0.co;2-m. PMID: 9096761
  12. Kool M, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014 Mar 17;25(3):393-405. PMID: 24651015
  13. Lo, Muzio, L, et al. Clinical utility gene card for: Gorlin syndrome--update 2013. Eur. J. Hum. Genet. 2013; 21(10):None. doi: 10.1038/ejhg.2012.299. PMID: 23361221
  14. Pastorino L, et al. Identification of a SUFU germline mutation in a family with Gorlin syndrome. Am J Med Genet A. 2009 Jul;149A(7):1539-43. PMID: 19533801
  15. Smith, MJ, et al. Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations. J. Clin. Oncol. 2014; 32(36):4155-61. PMID: 25403219

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