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, ovarian, or prostate 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).
IMPORTANT:
If you are ordering paired tumor testing for evaluation of mismatch repaired deficiency, order ColoSeq Tumor Panel [CSQTP].
If you are ordering paired polyp testing for the evaluation of gastrointestinal polyposis, order ColoSeq Polyposis [CSQP].
For an overview of available germline and paired tumor-germline testing for hereditary cancer syndromes, please see: Hereditary Cancer Test Menu: Germline and Paired Tumor-Germline guideline.
BROCA Paired Tumor Panel is not intended to evaluate for somatic mutations for purposes of cancer treatment. Analysis for these tests is limited to select somatic and constitutional mosaic mutations to aid in the diagnosis of genetic and/or hereditary conditions and not all somatic mutations detected are reported.
NOTE: A germline sample is required if germline BROCA or ColoSeq ™ testing was not performed previously at the University of Washington. The germline sample is used to evaluate for the presence of the apparently somatic mutations detected in the tumor, including the identification of constitutional mosaicism.
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, CDK4, CDK12, CDKN1B, CDKN2A, CEBPA, CHEK2, CTNNA1, CTNNB1, DDX41, DICER1, EGFR, EPCAM, ETV6, FANCM, FH, FLCN, GATA2, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1, MLH3, 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, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, SUFU, STK11, TMEM127, TP53, TSC1, TSC2, VHL, and WT1.
The assay completely sequences all exons and flanking introns of these genes and detects large deletions and duplications. Promoters and complete intronic sequencing of BRCA1, BRCA2 and the mismatch repair genes is performed, and non-coding variants of uncertain significance are assessed with RNA analysis when certain criteria are met. Next-generation sequencing is performed on an Illumina instrument to detect single nucleotide variants, insertions, deletions, gene amplifications, and selected translocations. BROCA Paired Tumor Panel is also useful for the detection of homologous recombination deficiency (prostate and ovarian cancer only) and microsatellite instability.*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.
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 CDKN1B
Cyclin-dependent kinase inhibitor 1B Parathyroid, Pituitary Multiple endocrine neoplasia, type IV CDKN2A
Cell cycle
Pancreatic, Melanoma
Familial melanoma and pancreatic cancer
CEBPA
Tumor suppressor
Leukemia
Familial AML 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
DDX41
Splicing regulation
Leukemia, MDS
Familial MDS, AML
DICER1
Tumor suppressor Wilms tumor, pleuropulmonary blastoma
DICER1 syndrome
EGFR
Epidermal growth factor receptor Lung
Familial lung cancer
EPCAM
Deletions inactivate MSH2, mismatch repair Colon, Ovarian, Endometrial
Lynch syndrome
ETV6
Transcription factor in hemopoietic regulation Leukemia, MDS Familial thrombocytopenia, MDS, acute leukemia
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.
GATA2
Transcription factor in hemopoietic regulation Leukemia, MDS
Familial leukemia, MDS, immunodeficiency
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 (parent-of-origin effect)
MBD4
Mismatch DNA repair
Uveal Melanoma, myelodysplastic 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 MSH2
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 PHOX2B
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 RUNX1
Hematopoietic stem cell regulation (transcription factor)
myelodysplastic syndrome and acute myeloid leukemia
RUNX1-familial platelet disorder
21148331 SDHA
Succinate dehydrogenase complex
Pheochromocytoma, Paraganglioma
Hereditary paraganglioma-pheochromoctyoma
20484225, 21752896 SDHAF2
Succinate dehydrogenase co-factor
Pheochromocytoma, Paraganglioma
Hereditary paraganglioma-pheochromoctyoma
20301715 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 SMARCE1
DNA repair and replication
Spinal meningioma
Familial spinal meningioma
23377182 STK11
Tumor suppressor
Breast, Colon, Pancreatic, Gastric, Hamartomas
Peutz-Jeghers syndrome
20301443 SUFU
Hedgehog Signaling
Basal cell carcinoma, medulloblastoma, meningioma, gonadal tumours
Nevoid basal cell-carcinoma syndrome (Gorlin syndrome)
19533801, 35768194 TMEM127
Tumor suppressor
Pheochromocytoma, Paraganglioma
Hereditary paraganglioma-pheochromocytoma
20301715 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 - 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
- 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].
- Synonyms
- AKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRAF, BRCA1, BRCA2, BRIP1, CDH1, CDK12, CDK4, CDKN1B, CDKN2A, CEBPA, CHEK2, CTNNA1, CTNNB1, DDX41, DICER1, EGFR, EPCAM, ETV6, FANCM, FH, FLCN, GATA2, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1, MLH3, 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, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, STK11, SUFU, TMEM127, 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 AKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRAF, BRCA1*, BRCA2*, BRIP1, CDH1, CDK4, CDK12, CDKN1B, CDKN2A, CEBPA, CHEK2, CTNNA1, CTNNB1, DDX41, DICER1, EGFR, EPCAM, ETV6, FANCM, FH, FLCN, GATA2, GEN1, GREM1, HOXB13, KIF1B, KIT, LZTR1, MAX, MBD4, MEN1, MET, MITF, MLH1*, MLH3, 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, RUNX1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, SMARCB1, SMARCE1, SUFU, STK11, TMEM127, 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
- 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
- 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.
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: 206-616-4584
Lab email: cgateam@uw.eduTel (EXOME only): 206-543-0459
Faculty
Jillian Buchan, PhD, FACMG
Runjun Kumar, MD, PhD
Regina Kwon, MD, MPH
Christina Lockwood, PhD, DABCC, DABMGG
Abbye McEwen, MD, PhD
Colin Pritchard, MD, PhD
Vera Paulson, MD, PhD
Eric Konnick, MD, MS
He Fang, PhD - Frequency
- Typical Turnaround: 4 weeks *Turn around times may vary based on factors such as tissue acquisition and insurance preauthorization.
- Available STAT?
- No
Billing & Coding
- CPT codes
- Billing Comments
For additional test/billing information, see following page, CPT codes for Hereditary Cancer Panels (germline and paired).
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
- Interfaced Order Code
- UOW3817