BROCA Paired Tumor Panel
General Information
- Lab Name
- BROCA Paired Tumor Panel
- Lab Code
- BROCOP
- Epic Ordering
-
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 ALK, AKT1, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1*, BRCA2*, BRIP1, CDH1, CDK4, CDK12, CDKN2A, CHEK1, CHEK2, CTNNA1, DICER1, EPCAM, FANCM, FH, GALNT12, GEN1, GREM1, MEN1, MET, MITF, MLH1*, MLH3, MRE11A, MSH2*, MSH6*, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOX2B, PIK3CA, PMS2*, POLD1, POLE, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SMAD4, SMARCA4, TP53, TSC1, TSC2, and VHL. The assay completely sequences all exons of these genes AND detects large deletions and duplications.
- 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 completely 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
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
Colon
Oligodontia-colorectal cancer syndrome
BAP1
BRCA1-associated protein complex
Uveal Melanoma, Mesothelioma
BARD1
BRCA1-associated protein complex
Breast, Ovarian
BMPR1A
TGF-beta signaling
Colon
Juvenile polyposis
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
CDK12
CDKN2A
Cell cycle
Pancreatic, Melanoma
CHEK1
Double stranded break repair
Unknown
CHEK2
Double stranded break repair
Breast
CTNNA1
Beta-catenin, e-cadherin complex
Gastric
Hereditary diffuse gastric cancer
DICER1
Wilms tumor, pleuropulmonary blastoma
DICER1 syndrome
FANCM
Breast
Fanconi anemia (recessive)
FH
Renal
Hereditary leiomyomatosis and renal cell cancer
GALNT12
O-glycosylation
Colon
GEN1
Double stranded break repair
Breast
GREM1
BMP antagonist
Colon
Hereditary mixed polyposis syndrome
MEN1
Gene expression regulation
Endocrine
Multiple endocrine neoplasia type 1
MET
Kidney, Squamous cell carcinomas
MITF
Kidney, Melanoma
MLH1
Mismatch DNA repair
Colon, Ovarian, Endometrial
Lynch syndrome
MLH3
Mismatch DNA repair
Polyposis (recessive)
MRE11A
Double stranded break repair
Breast
Ataxia-telangiectasia-like disorder (recessive)
MSH2 (+EPCAM)
Mismatch DNA repair
Colon, Ovarian, Endometrial
Lynch syndrome
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
Optic Glioma, Peripheral Nerve Sheath, Breast
Neurofibromatosis
NF2
Acoustic neuromas, Vestibular Schwannomas
Neurofibromatosis 2
NTHL1
Colon
Polyposis (recessive)
PALB2
Fanconi/BRCA
Breast, Pancreatic
Fanconi anaemia FA-N (recessive)
PDGFRA
GIST
PHOXB2
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
PRKAR1A
Endocrine
Carney complex (recessive)
PTCH1
Basal cell carcinoma, PNET
Nevoid basal cell-carcinoma syndrome
PTEN
PI3K/MAPK Signaling
Breast
Cowden syndrome
RAD51B
Double stranded break repair
Unknown
RAD51C
Fanconi/BRCA
Ovarian, Breast
Fanconi anaemia FA-O (recessive)
RAD51D
Fanconi/BRCA
Ovarian, Breast
Fanconi anaemia (recessive)
RB1
Retinoblastoma, Sarcoma, Melanoma
Hereditary retinoblastoma
RECQL
Breast
RET
Receptor Tyrosine Kinase
Endocrine
Multiple endocrine neoplasia type 2
RINT1
Breast, Colon
RPS20
Colon
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
Ovarian
TP53
Cell growth
Breast, Ovarian
Li-Fraumeni syndrome
TSC1
Hamartomas
Tuberous sclerosis complex
TSC2
Hamartomas
Tuberous sclerosis complex
VHL
p53 regulation
Kidney, Neuroendocrine
von Hippel-Lindau syndrome
*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, BART, BMPR1A, BRCA-negative reflex test, BRCA1, BRCA1&2 sequencing, BRCA2, breast cancer, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK1, CHEK2, CTNNA1, DICER1, DNA, EPCAM, FANCM, FH, GALNT12, GEN1, GREM1, Gynecological Oncology Pathway, GYNPTH, hereditary cancer panel, MEN1, MET, MITF, MLH1, MLH3, MRE11A, MSH2, MSH6, multi-gene panel, MUTYH, NBN, next-generation sequencing, NF1, NF2, NTHL1, ovarian cancer, paired tumor panel, PALB2, PDGFRA, PHOX2B, PIK3CA, PMS2, POLD1, POLE, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SMAD4, SMARCA4, TP53, TSC1, TSC2, VHL
- 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 ALK, AKT1, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDK12, CDKN2A, CHEK1, CHEK2, CTNNA1, DICER1, FANCM, FH, GALNT12, GEN1, GREM1,MEN1, MET, MITF, MLH1, MLH3, MRE11A, MSH2 (+EPCAM), MSH6, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PDGFRA, PHOXB1, PIK3CA, PMS2, POLD1, POLE, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SMAD4, SMARCA4, TP53, TSC1, TSC2, and VHL. Sequences are aligned to the human genome reference (hg19). 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
- Formalin-Fixed Paraffin Embedded Tumor Tissue (FFPE), Purified DNA, Peripheral Blood, cultured cells from skin biopsy, skin biopsy (direct), saliva, purified DNA from peripheral blood or cultured cells, saliva
- 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
- 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.
- Transport Temperature
Performance
- LIS Dept Code
- Genetics (GEN)
- Performing Location(s)
-
UW-MT Genetics Attention: Genetics Lab
Clinical lab, Room NW220
University of Washington Medical Center
1959 NE Pacific Street
Seattle, WA 98195Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-598–0304
Lab email: genelab@uw.eduTel (EXOME only): 206-543-0459
Manager
Joe Bernal, jbernal@uw.edu
Genetic Counselors
Angela Jacobson, MS, LGC agibson@uw.edu
Sandra Coe, MS,LGC, scoe20@uw.edu
Dru Leistritz, MS, LGC, dru2@uw.edu (EXOME testing only)
Daniel W. Serber, PhD, MS, LCGC, dwserber@uw.eduVariant Review Scientist
Ankita Jhuraney, PhD
Sarah Paolucci, MA, MS, LGC, spaolucc@uw.edu
Catherine A. Darcey, MScFaculty
Colin C. Pritchard, MD, PhD
Brian H. Shirts, MD, PhD
Christina Lockwood, PhD, DABCC
Stephen Salipante, MD, PhD
Eric Konnick, MD, MS
Niklas Krumm, MD,PhD
Vera Paulson, MD, PhD
Jillian Buchan, PhD, FACMG - 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
- 47997-2