• Test code: 01511
  • 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

Invitae Sarcoma Panel

Test description

This test analyzes up to 41 genes that are associated with a hereditary predisposition to the development of sarcomas—particularly bone and soft tissue sarcoma that can be found in any part of the body. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive hereditary sarcoma panel. Many of these genes are also associated with an increased risk of other cancer types.

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.

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Primary panel (26 genes)


Add-on Preliminary-evidence Genes for Sarcoma (5 genes)

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 genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.


Add-on Diamond-Blackfan Anemia Genes (10 genes)

Diamond-Blackfan anemia is a genetically heterogeneous condition that is characterized by anemia, congenital malformations, growth restriction, and an increased risk for leukemia and sarcoma. Genes associated with Diamond-Blackfan anemia may be added to this panel for patients with Diamond-Blackfan anemia-associated features at no additional charge.


  • Carney Stratakis syndrome
  • familial adenomatosis polyposis (FAP)
  • familial gastrointestinal stromal tumors (GIST)
  • hereditary paraganglioma pheochromocytoma (PGL/PCC)
  • Li Fraumeni syndrome (LFS)
  • neurofibromatosis
  • retinoblastoma

A sarcoma is a rare type of cancer that develops in connective tissue. Sarcomas can develop in a variety of tissues, such as bone, soft tissues, fat, muscle, nerves, fibrous tissues, blood vessels, deep skin tissues, and others. They most often develop in the limbs, but they can be found in any part of the body.

While most cases of sarcoma are sporadic and not inherited, several known genetic conditions are associated with an increased risk of sarcoma. Inherited pathogenic variants in certain genes, such as those included on this panel, account for some cases of hereditary sarcoma. Individuals with pathogenic variants in these genes have an increased risk of developing sarcomas and, in some cases, other cancers as well.

If a pathogenic variant is identified, this means there is an increased risk of malignancy compared to the average person, but not everyone with such a variant will develop cancer. Further, the same variant can cause different cancers—even among individuals within the same family. Because we cannot predict which cancers may develop, most people who are found to have a pathogenic variant will be offered various screening tests to detect and prevent cancer. For gene-associated cancer risks, see the table below.

GeneConditionSarcoma typeLifetime Risk
APC familial adenomatous polyposis (FAP), other APC-related conditions desmoid tumor 10%–20% (PMID: 8150351)
BLM Bloom syndrome connective tissue 2% ( Bloom’s syndrome registry )
CDKN1C Beckwith-Wiedemann syndrome rhabdomyosarcoma elevated (PMID: 16010495)
DICER1 DICER1 syndrome botryoid-type embryonal rhabdomyosarcoma, renal sarcoma elevated (PMID: 21205968, 24761742, 25022261)
EPCAM congenital mismatch repair deficiency (CMMR-D), Lynch syndrome* sarcoma elevated (PMID: 19130300, 22782591)
FH hereditary leiomyomatosis, renal cell cancer uterine leiomyosarcoma unknown (PMID: 16477632)
HRAS Costello syndrome rhabdomyosarcoma elevated (PMID: 11857556)
KIT familial gastrointestinal stromal tumors (GIST) gastrointestinal stromal tumors (GIST) elevated (PMID: 17193819, 23036227, 17943734)
MLH1 congenital mismatch repair deficiency (CMMR-D), Lynch syndrome* sarcoma elevated (PMID: 19130300, 22782591)
MSH2 congenital mismatch repair deficiency (CMMR-D), Lynch syndrome* sarcoma elevated (PMID: 19130300, 22782591)
MSH6 congenital mismatch repair deficiency (CMMR-D), Lynch syndrome* sarcoma elevated (PMID: 19130300, 22782591)
NBN Nijmegen breakage syndrome (NBS) rhabdomyosarcoma elevated (PMID: 15474156)
NF1 neurofibromatosis type 1 (NF1) gastrointestinal stromal tumors (GIST), malignant peripheral nerve sheath tumors (MPNST) up to 25% (PMID: 25130111, 20833335); 10% (PMID: 24535705)
PDGFRA familial gastrointestinal stromal tumors (GIST) gastrointestinal stromal tumors (GIST) unknown (PMID: 25975287)
PMS2 congenital mismatch repair deficiency (CMMR-D), Lynch syndrome* sarcoma elevated (PMID: 19130300, 22782591)
PRKAR1A Carney complex nerve sheath tumors 10%–14% (PMID: 10701527, 26130139)
PTCH1 basal cell nevus syndrome (Gorlin syndrome) fibrosarcoma, rhabdomyosarcoma elevated (PMID: 22691621, 6703200, 1347096)
RB1 retinoblastoma soft tissue sarcomas, osteosarcoma elevated (PMID: 22355046)
RECQL4 Rothmund-Thomson syndrome, Baller-Gerold syndrome, RAPADILINO syndrome osteosarcoma up to 30% (PMID: 11471165, 12952869)
SDHA familial gastrointestinal stromal tumors (GIST) gastrointestinal stromal tumors (GIST) elevated (PMID: 25741136)
SDHB familial gastrointestinal stromal tumors (GIST), Carney-Stratakis syndrome gastrointestinal stromal tumors (GIST) elevated (PMID: 25741136)
SDHC familial gastrointestinal stromal tumors (GIST), Carney-Stratakis syndrome gastrointestinal stromal tumors (GIST) elevated (PMID: 25741136)
SDHD familial gastrointestinal stromal tumors (GIST), Carney-Stratakis syndrome gastrointestinal stromal tumors (GIST) elevated (PMID: 25741136)
SUFU basal cell nevus syndrome (Gorlin syndrome) sarcoma unknown (PMID: 25403219)
TP53 Li-Fraumeni syndrome osteosarcoma, rhabdomyosarcoma 12%–21% (NCCN Guidelines. Soft Tissue Sarcoma. Version 1.2015).
WRN Werner syndrome soft tissue sarcomas, osteosarcoma elevated (PMID: 14676353)

*Sarcoma has been described in several patients with CMMRD due to biallelic pathogenic variants in mismatch repair genes, but the association of sarcoma with Lynch syndrome (monoallelic pathogenic variants) is based on limited evidence.

Elevated: There is evidence of association, but the penetrance and risk are not well characterized.
Unknown: Based on small studies, the risk is possibly increased, though not well-described.

Most of the genes on this panel confer an increased risk of developing sarcoma in an autosomal dominant inheritance pattern. The WRN, BLM, and NBN genes are associated with autosomal recessive Werner syndrome, Bloom syndrome, and Nijmegen breakage syndrome (NBS), respectively. MLH1, MSH2, MSH6, and PMS2 are associated with autosomal recessive constitutional mismatch repair deficiency (CMMR-D) and EPCAM is associated with autosomal recessive congenital tufting enteropathy (CTE).

This panel may be considered for individuals with a sarcoma. Other candidates for testing include those whose clinical and/or family history is suggestive of a hereditary sarcoma syndrome due to:

  • Li Fraumeni Syndrome
  • familial adenomatosis polyposis
  • hereditary paraganglioma pheochromocytoma
  • familial gastrointestinal stromal tumor (GIST)
  • Carney Stratakis syndrome
  • retinoblastoma
  • neurofibromatosis

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)

  1. American Cancer Society, Cancer.org: What is a soft tissue sarcoma? http://www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-soft-tissue-sarcoma Accessed September 2015.
  2. Antonescu, CR. Gastrointestinal stromal tumor (GIST) pathogenesis, familial GIST, and animal models. Semin Diagn Pathol. 2006; 23(2):63-9. doi: 10.1053/j.semdp.2006.08.003. PMID: 17193819
  3. Armada, RC, et al. Embryonal rhabdomyosarcoma associated with tuberous sclerosis. Med. Pediatr. Oncol. 2002; 38(4):302. PMID: 11920808
  4. Cohen, MM. Beckwith-Wiedemann syndrome: historical, clinicopathological, and etiopathogenetic perspectives. Pediatr. Dev. Pathol. 2005; 8(3):287-304. PMID: 16010495
  5. Farndon, PA, et al. Location of gene for Gorlin syndrome. Lancet. 1992; 339(8793):581-2. PMID: 1347096
  6. Finch, T, et al. Gorlin syndrome presenting with a unilateral ovarian fibroma in a 22-year-old woman: a case report. J Med Case Rep. 2012; 6:148. PMID: 22691621
  7. Gonzalez, KD, et al. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J. Clin. Oncol. 2009; 27(8):1250-6. doi: 10.1200/JCO.2008.16.6959. PMID: 19204208
  8. Gripp, KW, et al. Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol. Am. J. Med. Genet. 2002; 108(1):80-7. PMID: 11857556
  9. Gurbuz, AK, et al. Desmoid tumours in familial adenomatous polyposis. Gut. 1994; 35(3):377-81. doi: 10.1016/0959-8049(94)90655-6. PMID: 8150351
  10. Kleinbaum, EP, et al. Clinical, histopathologic, molecular and therapeutic findings in a large kindred with gastrointestinal stromal tumor. Int. J. Cancer. 2008; 122(3):711-8. doi: 10.1002/ijc.23137. PMID: 17943734
  11. Kleinerman, RA, et al. Variation of second cancer risk by family history of retinoblastoma among long-term survivors. J. Clin. Oncol. 2012; 30(9):950-7. PMID: 22355046
  12. Kraemer, BB, et al. Fibrosarcoma of ovary. A new component in the nevoid basal-cell carcinoma syndrome. Am. J. Surg. Pathol. 1984; 8(3):231-6. PMID: 6703200
  13. Meyer, S, et al. Rhabdomyosarcoma in Nijmegen breakage syndrome: strong association with perianal primary site. Cancer Genet. Cytogenet. 2004; 154(2):169-74. PMID: 15474156
  14. Postow, MA, Robson, ME. Inherited gastrointestinal stromal tumor syndromes: mutations, clinical features, and therapeutic implications. Clin Sarcoma Res. 2012; 2(1):16. doi: 10.1186/2045-3329-2-16. PMID: 23036227
  15. Ricci, R, et al. PDGFRA-mutant syndrome. Mod. Pathol. 2015; 28(7):954-64. doi: 10.1038/modpathol.2015.56. PMID: 25975287
  16. Siitonen, HA, et al. Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases. Hum. Mol. Genet. 2003; 12(21):2837-44. PMID: 12952869
  17. Weill Cornell Medical College, Bloom’s Syndrome Registry: http://weill.cornell.edu/bsr/data_from_registry/ Accessed August 2015.
  18. Yamamoto, K, et al. A report of two cases of Werner's syndrome and review of the literature. J Orthop Surg (Hong Kong). 2003; 11(2):224-33. PMID: 14676353
  19. Ylisaukko-oja, SK, et al. Analysis of fumarate hydratase mutations in a population-based series of early onset uterine leiomyosarcoma patients. Int. J. Cancer. 2006; 119(2):283-7. PMID: 16477632

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 in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

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
APC* NM_000038.5
BLM NM_000057.3
CDKN1C NM_000076.2
CDKN2A* NM_000077.4; NM_058195.3
DICER1 NM_177438.2
EPCAM* NM_002354.2
FH NM_000143.3
GATA1 NM_002049.3
HRAS NM_005343.2
KIT NM_000222.2
MLH1* NM_000249.3
MSH2* NM_000251.2
MSH6 NM_000179.2
NBN NM_002485.4
NF1 NM_000267.3
PDGFRA NM_006206.4
PMS2 NM_000535.5
POT1 NM_015450.2
PRKAR1A NM_002734.4
PTCH1 NM_000264.3
PTCH2 NM_003738.4
RB1 NM_000321.2
RECQL4 NM_004260.3
RPL11 NM_000975.3
RPL26 NM_000987.3
RPL35A NM_000996.2
RPL5 NM_000969.3
RPS10 NM_001014.4
RPS19 NM_001022.3
RPS24 NM_033022.3
RPS26 NM_001029.3
RPS7 NM_001011.3
SDHA* NM_004168.3
SDHB NM_003000.2
SDHC NM_003001.3
SDHD NM_003002.3
SUFU NM_016169.3
TP53* NM_000546.5
TSC1 NM_000368.4
TSC2 NM_000548.3
WRN* NM_000553.4

APC: The 1B promoter region is covered by both sequencing and deletion/duplication analysis. The 1A promoter region is covered by deletion/duplication analysis.
CDKN2A: Analysis supports interpretation of the p14 and p16 proteins.
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).
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.