BROCA Paired Tumor Panel
General Information
Lab Name
BROCA Paired Tumor Panel
Lab Code
BROCOP
Epic Name
Order using "UW Genetics and Solid Tumor Test Request"
Place a separate order to draw the paired blood sample.
See tip sheet for more information (internal link).
Description
BROCA Paired Tumor Panel is useful for the evaluation of both somatic and germline variants, including patients with a suspected hereditary cancer predisposition, with a focus on syndromes that include breast or ovarian cancer as one of the cancer types. Depending on the causative gene involved, these cancers may co-occur with other cancer types (such as colorectal, endometrial, pancreatic, endocrine, or melanoma).
BROCA Tumor uses next-generation sequencing to detect most mutations in AKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRAF, BRCA1*, BRCA2*, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CTNNA1, CTNNB1, DICER1, ENG, EPCAM, FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1*, MLH3, MRE11, MSH2*, MSH3, MSH6*, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PIK3CA, PMS2*, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RNF43, RPS20, RSPO3, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SUFU, TP53, TSC1, TSC2, VHL, WT1.
The assay completely sequences all exons of these genes AND detects large deletions and duplications.
*For genes with an asterisk in the list above, intronic regions are also sequenced and analyzed.
- BROCA Paired Tumor Panel is also useful for the detection of actionable somatic (tumor) mutations, such as somatic BRCA1/2 and PIK3CA mutations, as well as homologous recombination deficiency (ovarian cancer only) and microsatellite instability.
- The test uses next-generation sequencing to detect mutations in the genes listed in the table below. The assay sequences all exons, select promoter regions of these genes and detects single nucleotide variants, small insertions and deletions (indels), large deletions, duplications, constitutional and somatic mosaicism. For genes indicated with *above, intronic regions are sequenced and analyzed.
- See BROCA Cancer Risk Panel [BROCA] for germline only testing.
- Single Gene Analysis [SGN] (next generation sequencing) can be ordered for any gene on the BROCA panel.
- Known Mutation Testing [KMU] testing can be requested for relatives of probands with pathogenic/likely pathogenic mutations previously detected in via testing at the UW Genetics Laboratory. Known mutation testing can also be requested for patients where mutations were detected, in UW Genetics Laboratory somatic testing, that are suspected to be germline.
- Custom BROCA can be ordered by specifying genes for which testing is requested on the Genetics Requisition; pricing is the same as full BROCA Paired Tumor Panel.
- For patients with a suspected hereditary colon cancer syndrome, see ColoSeq - Lynch and Polyposis Panel [COSEQ] or ColoSeq Tumor Panel [CSQTP].
|
Gene |
Function/Pathway |
Heterozygote Cancer risk* |
Associated syndrome |
References (PMID) |
|
ALK |
MYC signaling |
Neuroblastoma |
Cowden-like | |
|
AKT1 |
AKT signaling |
Breast, Thyroid |
Cowden-like |
|
|
APC |
WNT signaling |
Colon |
Familial adenomatous polyposis |
|
|
ATM |
Double stranded break repair |
Breast, Pancreatic |
Ataxia telangiectasia (recessive) |
|
|
ATR |
Double stranded break repair |
Oropharyngeal |
Seckel (recessive) |
|
|
AXIN2 |
WNT signaling |
Colon |
Oligodontia-colorectal cancer syndrome |
|
|
BAP1 |
BRCA1-associated protein complex |
Uveal Melanoma, Mesothelioma |
BAP1 Tumor predisposition syndrome | |
|
BARD1 |
BRCA1-associated protein complex |
Breast, Ovarian |
Hereditary breast cancer | |
|
BMPR1A |
TGF-beta signaling |
Colon |
Juvenile polyposis |
|
|
BRAF |
Serine/Threonine protein kinase |
Typically somatic or mosaic only |
Typically somatic only, association with MLH1 promoter hypermethylation in colon cancer and Cardiofaciocutaneous syndrome when mosaic |
|
|
BRCA1 |
BRCA1-associated protein complex |
Breast, Ovarian |
Hereditary breast and ovarian cancer |
|
|
BRCA2 |
Fanconi/BRCA |
Breast, Ovarian |
Hereditary breast and ovarian cancer, Fanconi anaemia FA-D1 (recessive) |
|
|
BRIP1 |
Fanconi/BRCA |
Breast, Ovarian |
Fanconi anaemia FA-J (recessive) |
|
|
CDH1 |
Cell adhesion |
Breast, Gastric |
Hereditary diffuse gastric cancer |
|
|
CDK4 |
Cell cycle |
Melanoma |
Familial melanoma | |
|
CDK12 |
MAP kinase regulation | Breast, ovarian cancer, frequently somatic | Hereditary breast and ovarian cancer | |
|
CDKN2A |
Cell cycle |
Pancreatic, Melanoma |
Familial melanoma and pancreatic cancer | |
|
CHEK2 |
Double stranded break repair |
Breast |
Hereditary breast cancer | |
|
CTNNA1 |
Beta-catenin, e-cadherin complex |
Gastric |
Hereditary diffuse gastric cancer |
|
|
CTNNB1 |
WNT signaling |
Typically somatic only |
Colon cancer, endometrial cancer, desmoid tumors, colon adenomas |
|
|
DICER1 |
Tumor suppressor |
Wilms tumor, pleuropulmonary blastoma |
DICER1 syndrome |
|
|
ENG |
Transforming growth factor-beta (TGFB) receptor complex and binds TGFB1 |
Colon polyps, telangiectasia |
Hereditary Hemorrahagic Telangiectasia, type 1), potential colon polyposis syndrome |
|
|
FANCM |
Fanconi/BRCA |
Breast |
Fanconi anemia (recessive) |
|
|
FH |
Tumor suppressor |
Renal |
Hereditary leiomyomatosis and renal cell cancer |
|
|
FLCN |
Tumor suppressor |
Renal |
Birt-Hogg-Dube syndrome. Primary spontaneous pneumothorax. |
|
|
GALNT12 |
O-glycosylation |
Colon |
unknown | |
|
GEN1 |
Double stranded break repair |
Breast |
Hereditary breast cancer | |
|
GREM1 |
BMP antagonist |
Colon |
Hereditary mixed polyposis syndrome |
|
|
HOXB13 |
Sequence-specific transcription factor which binds preferentially to methylated DNA |
Prostate |
Familial prostate cancer |
36446039, 34799695, 34059701 |
|
KIF1B |
Tumor suppressor |
Neuroblastoma |
Hereditary neuroblastoma | 18334619, 24469107, 30859632 |
|
KIT |
Proto-oncogene which encodes a tyrosine-protein kinase that acts as a cell-surface receptor for cytokine KITLG/SCF |
Gastrointestinal stromal tumors (GIST), Acute myelogenous leukemia (AML) |
Hereditary GIST and AML |
36351335, 35821557 |
|
LZTR1 |
RAS ubiquitination/MAPK signaling |
Schwannomatosis |
Schwannomatosis, Noonan syndrome |
|
|
MAX |
MYC signaling |
Pheochromocytoma, Paraganglioma |
Hereditary pheochromocytoma and paraganglioma |
|
|
MBD4 |
Mismatch DNA repair |
Uveal Melanoma, myelodyplastic disease, colon polyposis |
Polyposis, multi-organ tumor predisposition (recessive) |
|
|
MEN1 |
Gene expression regulation |
Endocrine |
Multiple endocrine neoplasia type 1 |
|
|
MET |
Tyrosine Kinase receptor |
Kidney, Squamous cell carcinomas |
Hereditary papillary renal cell carcinoma | |
|
MITF |
Melanocyte inducing transcription factor |
Kidney, Melanoma |
MITF-related melanoma and renal cell carcinoma predisposition | |
|
MLH1 |
Mismatch DNA repair |
Colon, Ovarian, Endometrial |
Lynch syndrome |
|
|
MLH3 |
Mismatch DNA repair |
Polyposis (recessive) |
unknown | |
|
MRE11A |
Double stranded break repair |
Breast |
Ataxia-telangiectasia-like disorder (recessive) |
|
|
MSH2 (+EPCAM) |
Mismatch DNA repair |
Colon, Ovarian, Endometrial |
Lynch syndrome |
|
|
MSH3 |
Mismatch DNA repair |
Polyposis |
Familial adenomatous polyposis 4 (recessive) |
|
|
MSH6 |
Mismatch DNA repair |
Colon, Endometrial |
Lynch syndrome |
|
|
MUTYH |
DNA repair |
Colon (homozygotes) |
MUTYH-associated polyposis |
|
|
NBN |
Double stranded break repair |
Breast |
Nijmegen breakage syndrome (recessive) |
|
|
NF1 |
MAPK signaling |
Optic Glioma, Peripheral Nerve Sheath, Breast |
Neurofibromatosis |
|
|
NF2 |
Cellular regulation |
Acoustic neuromas, Vestibular Schwannomas |
Neurofibromatosis 2 |
|
|
NTHL1 |
Base excision repair |
Colon |
Polyposis (recessive) |
|
|
PALB2 |
Fanconi/BRCA |
Breast, Pancreatic |
Fanconi anaemia FA-N (recessive) |
|
|
PDGFRA |
Protein tyrosine kinase |
GIST |
Familial, sporadic GIST | |
|
PHOXB2 |
Tumor suppressor |
Neuroblastoma |
Hereditary neuroblastoma | |
|
PIK3CA |
AKT signaling |
Breast, Thyroid |
Cowden-like |
|
|
PMS2 |
Mismatch DNA repair |
Colon, Endometrial |
Lynch syndrome |
|
|
POLD1 |
DNA Polymerase |
Colon, Endometrial |
Familial polyposis, colorectal cancer |
|
|
POLE |
DNA Polymerase |
Colon |
Familial polyposis, colorectal cancer |
|
|
POT1 |
Telomere maintenance |
Melanoma, CLL, Sarcoma, Glioma, Colon, Thyroid, Breast |
Multi-organ tumor predisposition |
|
|
PRKAR1A |
cAMP signaling |
Endocrine |
Carney complex (recessive) |
|
|
PTCH1 |
Hedgehog |
Basal cell carcinoma, PNET |
Nevoid basal cell-carcinoma syndrome |
|
|
PTEN |
PI3K/MAPK Signaling |
Breast |
Cowden syndrome |
|
|
RAD51B |
Double stranded break repair |
Unknown |
Hereditary breast and ovarian cancer | |
|
RAD51C |
Fanconi/BRCA |
Ovarian, Breast |
Fanconi anaemia FA-O (recessive) |
|
|
RAD51D |
Fanconi/BRCA |
Ovarian, Breast |
Fanconi anaemia (recessive) |
|
|
RB1 |
Tumor suppressor |
Retinoblastoma, Sarcoma, Melanoma |
Hereditary retinoblastoma |
|
|
RECQL |
DNA repair |
Breast |
Hereditary breast cancer | |
|
RET |
Receptor Tyrosine Kinase |
Endocrine |
Multiple endocrine neoplasia type 2 |
|
|
RINT1 |
DNA checkpoint regulation |
Breast, Colon |
Multi-organ tumor predisposition | |
|
RNF43 |
WNT signaling |
Colon |
Sessile Serrated Polyposis | 27329244, 27081527 |
|
RPS20 |
Ribosomal protein |
Colon |
unknown | |
|
RSPO3 |
WNT signaling |
Typically somatic only |
Colon cancer | 29127379, 37048063 |
|
SDHA |
Succinate dehydrogenase complex |
Pheochromocytoma, Paraganglioma |
Hereditary paraganglioma-pheochromoctyoma |
20484225, 21752896 |
|
SDHB |
Succinate dehydrogenase complex |
Pheochromocytoma, Paraganglioma |
Hereditary paraganglioma-pheochromoctyoma |
|
|
SDHC |
Succinate dehydrogenase complex |
Pheochromocytoma, Paraganglioma |
Hereditary paraganglioma-pheochromoctyoma |
|
|
SDHD |
Succinate dehydrogenase complex |
Pheochromocytoma, Paraganglioma |
Hereditary paraganglioma-pheochromoctyoma |
|
|
SMAD4 |
TGF-beta signaling |
Colon |
Juvenile polyposis |
|
|
SMARCA4 |
SWI/SNF complex |
Ovarian |
Hereditary small cell carcinoma of the ovary, hypercalcemic | |
|
SMARCB1 |
ATP-dependent SWI/SNF chromatin remodeling complex |
Schwannoma, Pediatric Rhabdoid Tumors (Kidney, CNS, Soft Tissue), Meningioma, |
Schwannomatosis, rhabdoid tumor predisposition syndrome type 1 |
28109176, 29706634 |
|
SUFU |
Hedgehog Signaling |
Basal cell carcinoma, medulloblastoma, meningioma, gonadal tumours |
Nevoid basal cell-carcinoma syndrome (Gorlin syndrome) |
19533801, 35768194 |
|
TP53 |
Cell growth |
Breast, Ovarian |
Li-Fraumeni syndrome |
|
|
TSC1 |
Cell growth |
Hamartomas |
Tuberous sclerosis complex |
|
|
TSC2 |
Cell growth |
Hamartomas |
Tuberous sclerosis complex |
|
|
VHL |
p53 regulation |
Kidney, Neuroendocrine |
von Hippel-Lindau syndrome |
|
|
WT1 |
WT1 transcription factor |
Wilms tumor |
Wilms tumor |
15150775 |
*Only the most commonly associated cancer types are listed. A more detailed description of cancer risk for some BROCA genes can be found at GeneReviews.
References
- Walsh T, et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci U S A 2010, 107:12629-33. 20616022
- Walsh T, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A 2011, 108:18032-7. 22006311
- Nord AS, Lee M, King MC, and Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics 2011, 12:184. 21486468
- Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet 2010, 11:31-46. 19997069
- Shirts BH, et al. Improving performance of multigene panels for genomic analysis of cancer predisposition. Genet Med 2016, 18:974-81. 26845104
Synonyms
AKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRAF, BRCA1*, BRCA2*, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CTNNA1, CTNNB1, DICER1, ENG, EPCAM, FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1*, MLH3, MRE11, MSH2*, MSH3, MSH6*, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PIK3CA, PMS2*, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RNF43, RPS20, RSPO3, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SUFU, TP53, TSC1, TSC2, VHL, WT1
Components
| Code | Name |
|---|---|
| BROPGS | BROCA Tumor Genes Sequenced |
| BROPRE | BROCA Tumor Result |
| BROPIN | BROCA Tumor Interpretation |
| BROPCH | BROCA Tumor Clinical History |
| BROPMT | BROCA Tumor Methods |
| BROPDI | BROCA Tumor Director |
Interpretation
Method
Next-generation sequencing.
This assay sequences all exons and flanking intronic splice site sequences of AAKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRAF, BRCA1*, BRCA2*, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CTNNA1, CTNNB1, DICER1, ENG, EPCAM, FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1*, MLH3, MRE11, MSH2*, MSH3, MSH6*, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PIK3CA, PMS2*, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RNF43, RPS20, RSPO3, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SUFU, TP53, TSC1, TSC2, VHL, and WT1. Gene introns are also sequenced for genes indicated above with an asterisk (*). Sequences are aligned to the human genome reference (HG38). Test performed by targeted capture for listed genes followed by next-generation sequencing with Illumina technology. This test was developed and its performance characteristics determined by the University of Washington Department of Laboratory Medicine. It has not been cleared or approved by the US Food and Drug Administration. This laboratory is certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. This test is used for clinical purposes. It should not be regarded as investigational or for research.
Reference Range
See individual components
Guidelines
Ordering & Collection
Specimen Type
Collection
NOTE: This test requires BOTH tumor tissue and a germline sample such as peripheral blood.
Tumor Tissue:
Tumor specimen will be requested directly, by UW Laboratory Medicine & Pathology, from the originating pathology department. In order to facilitate this, a pathology report should be submitted with the test requisition, blood control and other clinical and billing paperwork.
If the tumor specimen is being submitted by the ordering provider, tissue samples (FFPE) either (a) slides, OR (b) tissue block are required.
(a) Instructions for slide specimens: 1 slide at 4-micron thickness stained with hematoxylin-and-eosin AND 20 unstained, non-baked slides at 10-micron thickness (a minimum of 10 unstained slides is acceptable). Unstained slides can be on charged or uncharged slides. Note: Sections should contain as much tumor tissue as possible.
(b) Instructions for tissue block specimen: Provide complete tissue block containing tumor tissue. If there is more than one tissue block, please provide the block that has the greatest amount of tumor tissue. Tissue block will be returned at completion of testing. Ship at room temperature.
Germline sample:
BLOOD:
Preferred: 5 mL whole blood in LAVENDER TOP EDTA tube.
Also acceptable: YELLOW TOP ACD tube, purified DNA from peripheral blood or cultured cells.
SKIN BIOPSY:
Collection and transport: Obtain 2-4 mm punch biopsy of skin sample under sterile conditions and place in transport media (e.g. Alpha-MEM media, RPMI). Transport media can be supplied by the lab; call 206-598-4488 to request. If transport media is not available, the following media are acceptable alternatives if shipping time will not exceed 24 hours: lactated Ringer's solution, viral transport medium, or sterile saline. DO NOT USE formaldehyde, formalin, alcohol, or 5% dextrose, or tissue culture medium buffered with bicarbonate.
CULTURED CELLS:
(2) T23 or (1) T75 flask (minimum 1-T25 flask).
SALIVA:
Contact laboratory for validated collection kit.
Forms & Requisitions
Genetics preauthorization form (preauthorization is only done for providers who are external to the UW system).
1. Fill out a Genetics Requisition form.
Providers with access to the UW implementation of Epic (i.e., FHCC, HMC, SCCA, UWMC, UWNW) may order this test using the order "UW Genetics and Solid Tumor Test Request." See tip sheet for more information.
2. Under "Check Test Requested," check: "BROCA Paired Tumor Panel".
3. For single gene next-generation sequencing or known muatation testing, see Single Gene Analysis [SGN] or Known Mutation Testing [KMU].
Handling Instructions
Ship specimen at room temperature for overnight delivery.
Blood specimens can be held for up to 7 days before shipping if refrigerated.
Ship specimens to:
UW MEDICAL CENTER
LABORATORY MEDICINE - GENETICS LAB
1959 NE PACIFIC ST, ROOM NW220
SEATTLE, WA 98195-7110
Quantity
requested: Entire sample
minimum: 5mL whole blood
Processing
Blood: Refrigerate whole blood
Unacceptable Conditions: Frozen or clotted specimens
Stability (collection to initiation of testing): Ambient: 5 days; Refrigerated: 7 days; Frozen: Unacceptable
Purified DNA: Refrigerate DNA specimens. Frozen is acceptable.
Performance
LIS Dept Code
Genetics (GEN)
Performing Location(s)
| UW-MT |
Genetics
Attention: Genetics Lab Tel: 206-598–6429 M–F (7:30 AM–4:00 PM) Tel (EXOME only): 206-543-0459 |
Manager Variant Review Scientist Faculty |
|---|
Frequency
Results within 3-4 weeks, once sample arrives in the laboratory.
Available STAT?
No
Billing & Coding
CPT codes
Billing Comments
For additional test/billing information, see following page: BROCA Cancer Risk Panel billing information.
For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.
Billing and Insurance Pre-Authorization
We offer insurance pre-authorization services (preauthorization is only done for providers who are external to the UW system).
Email: gpab@uw.edu or call 1-855-320-4869 for more information.
LOINC
Interfaced Order Code
UOW3817