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  • Test code: 01511
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    3mL whole blood in a purple-top tube
  • Alternate specimens:
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Invitae Sarcoma Panel

Test description

The Invitae Sarcoma Panel analyzes genes associated with a hereditary predisposition to the development of sarcomas, a type of connective tissue tumor that can occur anywhere in 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.

The primary panel includes 28 genes associated with sarcoma. In addition to the primary panel, clinicians can also choose to include 5 genes that have preliminary evidence of an association with this cancer type. At this time, the association of these genes with sarcoma remains uncertain; however, some clinicians may wish to include genes that may prove to be clinically significant in the future. These genes can be added at no additional charge.

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 (28 genes)

APC BLM CDKN1C DICER1 EPCAM EXT1 EXT2 FH HRAS KIT MLH1 MSH2 MSH6 NBN NF1 PDGFRA PMS2 PRKAR1A PTCH1 RB1 RECQL4 SDHA SDHB SDHC SDHD SUFU TP53 WRN

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

Genes with preliminary evidence of association with hereditary sarcoma are available to add on to the primary panel. Adding on preliminary-evidence genes can increase the number of variants of uncertain significance that are identified. 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. Visit our Preliminary-evidence genes page to learn more.

CDKN2A POT1 PTCH2 TSC1 TSC2

Add-on Diamond-Blackfan Anemia Genes (13 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 at no additional charge.

GATA1 RPL11 RPL15 RPL19 RPL26 RPL35A RPL5 RPS10 RPS19 RPS24 RPS26 RPS29 RPS7

  • Li-Fraumeni syndrome (LFS)
  • familial adenomatosis polyposis (FAP)
  • hereditary paraganglioma pheochromocytoma (PGL/PCC)
  • familial gastrointestinal stromal tumors (GIST)
  • Beckwith-Wiedemann syndrome
  • Carney complex
  • Carney-Stratakis syndrome
  • hereditary retinoblastoma
  • neurofibromatosis type 1
  • constitutional mismatch repair deficiency (CMMR-D)
  • hereditary leiomyomatosis and renal cell carcinoma (HLRCC)
  • hereditary multiple osteochondromas
  • Werner syndrome
  • Rothmund-Thomson syndrome, Baller-Gerold syndrome, RAPADILINO syndrome
  • Gorlin syndrome (nevoid basal cell carcinoma syndrome)
  • Nijmegen breakage syndrome
  • Bloom syndrome
  • fumarate hydratase deficiency
  • mitochondrial complex II deficiency

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 and deep skin tissues. They most often develop in the limbs, but 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.

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 may manifest with different symptoms, even among family members. Because we cannot predict which cancers may develop, additional medical management strategies focused on cancer prevention and early detection may be beneficial. 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)
EXT1, EXT2 hereditary multiple osteochondromas osteochondrosarcoma 3%-20% (PMID: 18853760, 16897210)
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 CMMR-D 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 have autosomal dominant inheritance. Several also have autosomal recessive inheritance, or result in clinically distinct autosomal recessive conditions, as outlined below:

  • WRN is associated with Werner syndrome
  • NBN is associated with Nijmegen breakage syndrome
  • BLM is associated with Bloom syndrome
  • FH is associated with fumarate hydratase deficiency
  • MLH1, MSH2, MSH6 and PMS2 are associated with constitutional mismatch repair deficiency syndrome (CMMR-D)
  • RECQL4 is associated with Rothmund-Thomson, Baller-Gerold, and RAPADILINO syndromes
  • SDHA and SDHB are associated with mitochondrial complex II deficiency

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 (PGL-PCC)
  • Gorlin syndrome
  • Carney complex
  • familial gastrointestinal stromal tumor (GIST)
  • retinoblastoma
  • neurofibromatosis type 1

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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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.

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
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
EXT1 NM_000127.2
EXT2 NM_207122.1
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
RPL15 NM_002948.3
RPL19 NM_000981.3
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
RPS29 NM_001032.4
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.