BROCA Cancer Risk Panel

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General Information

Lab Name
BROCA Cancer Risk Panel
Lab Code
BROCA
Epic Ordering
BROCA Cancer Risk Panel
Description

BROCA is useful for the evaluation of 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 uses next-generation sequencing to detect most pathogenic variants in

ALK, APC*, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1*, BRCA2*, BRIP1, CDH1, CDK4, CDK12, CDKN2A, CHEK2, CTNNA1, DICER1, EPCAM, FANCM, FH, FLCN, GEN1, GREM1, HOXB13, MEN1, MET, MITF, MLH1*, MLH3, MSH2*, MSH3, MSH6*, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PHOX2B, PIK3CA, PMS2*, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RNF43, 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.

  • See BROCA Paired Tumor Panel [BROCOP] for tumor, germline paired 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 variants previously detected via testing at the UW Genetics Laboratory.
  • For Ashkenazi Jewish patients, testing for the three BRCA1/2 founder variants are available, see BRCA1&2 Ashkenazi Mutations [BRCAAJ].
  • For patients with suspected hereditary colon cancer syndrome, see ColoSeq - Lynch and Polyposis Panel [COSEQ].
  • The test uses next-generation sequencing to detect mutations in the genes listed in the table below. The assay completely sequences all exons, selects 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.
  • Custom BROCA can be ordered by specifying genes for which testing is requested on the Genetics Requisition; pricing is the same as the full BROCA Cancer Risk Panel.

BROCA Gene List

Gene

Function/Pathway

Heterozygote Cancer risk*

Associated syndrome

References (PMID)

ALK

MYC signaling

Neuroblastoma

18724359, 28674118

APC

WNT signaling

Colon

Familial adenomatous polyposis

20301519

ATM

Double stranded break repair

Breast, Pancreatic

Ataxia telangiectasia (recessive)

16832357, 19781682, 22585167

ATR

Double stranded break repair

Oropharyngeal

Seckel (recessive)

22341969

AXIN2

Colon

Oligodontia-colorectal cancer syndrome

15042511

BAP1

BRCA1-associated protein complex

Uveal Melanoma, Mesothelioma

21874000, 21874003

BARD1

BRCA1-associated protein complex

Breast, Ovarian

21344236

BMPR1A

TGF-beta signaling

Colon

Juvenile polyposis

20301642

BRCA1

BRCA1-associated protein complex

Breast, Ovarian

Hereditary breast and ovarian cancer

22006311, 2270482, 7545954

BRCA2

Fanconi/BRCA

Breast, Ovarian

Hereditary breast and ovarian cancer, Fanconi anaemia FA-D1 (recessive)

22006311, 8524414

BRIP1

Fanconi/BRCA

Breast, Ovarian

Fanconi anaemia FA-J (recessive)

22006311, 17033622, 21964575

CDH1

Cell adhesion

Breast, Gastric

Hereditary diffuse gastric cancer

20301318

CDK4

Cell cycle

Melanoma

19585149

CDK12

24554720, 29906450, 24240700

CDKN2A

Cell cycle

Pancreatic, Melanoma

19585149

CHEK2

Double stranded break repair

Breast

11967536

CTNNA1

Beta-catenin, e-cadherin complex

Gastric

Hereditary diffuse gastric cancer

23208944

DICER1

Wilms tumor, pleuropulmonary blastoma

DICER1 syndrome

29343557, 28960912, 23625684

FANCM

Breast

Fanconi anemia (recessive)

25288723

FH

Renal

Hereditary leiomyomatosis and renal cell cancer

25018647, 11865300, 25004247

FLCN

Renal

Birt-Hogg-Dube syndrome

12204536, 20301695

GEN1

Double stranded break repair

Breast

2052659

GREM1

BMP antagonist

Colon

Hereditary mixed polyposis syndrome

22561515

HOXB13

transcription factor

Prostate

22236224

MEN1

Gene expression regulation

Endocrine

Multiple endocrine neoplasia type 1

9215689

MET

Kidney, Squamous cell carcinomas

11551094, 9140397, 27330189

MITF

Kidney, Melanoma

24290354, 22012259

MLH1

Mismatch DNA repair

Colon, Ovarian, Endometrial

Lynch syndrome

20301390

NEW MLH3

Mismatch DNA repair

Polyposis (recessive)

30573798

MSH2 (+EPCAM)

Mismatch DNA repair

Colon, Ovarian, Endometrial

Lynch syndrome

20301390

MSH3

Polyposis (recessive)

27476653

MSH6

Mismatch DNA repair

Colon, Endometrial

Lynch syndrome

20301390

MUTYH

DNA repair

Colon (homozygotes)

MUTYH-associated polyposis

20301519, 21952991

NBN

Double stranded break repair

Breast

Nijmegen breakage syndrome (recessive)

15185344, 9590180

NF1

Optic Glioma, Peripheral Nerve Sheath, Breast

Neurofibromatosis

2114220, 23165953, 20301288

NF2

Acoustic neuromas, Vestibular Schwannomas

Neurofibromatosis 2

20301380

NTHL1

Colon

Polyposis (recessive)

25938944, 26431160

PALB2

Fanconi/BRCA

Breast, Pancreatic

Fanconi anaemia FA-N (recessive)

17200668, 17200671, 25099575

PHOXB2

Neuroblastoma

17637745, 28674118

PIK3CA

AKT signaling

Breast, Thyroid

Cowden-like

22729224, 23246288

PMS2

Mismatch DNA repair

Colon, Endometrial

Lynch syndrome

20301390

POLD1

DNA Polymerase

Colon, Endometrial

Familial polyposis, colorectal cancer

23263490, 23770608

POLE

DNA Polymerase

Colon

Familial polyposis, colorectal cancer

23263490

POT1

Brain, Melanoma

Familial melanoma and brain cancer

25482530, 24686849

PRKAR1A

Endocrine

Carney complex (recessive)

4010501

PTCH1

Basal cell carcinoma, PNET

Nevoid basal cell-carcinoma syndrome

8681379, 8658145, 20301330

PTEN

PI3K/MAPK Signaling

Breast

Cowden syndrome

20301661

RAD51B

Double stranded break repair

Unknown

24139550

RAD51C

Fanconi/BRCA

Ovarian, Breast

Fanconi anaemia FA-O (recessive)

22006311, 22538716

RAD51D

Fanconi/BRCA

Ovarian, Breast

21822267, 22415235

RB1

Retinoblastoma, Sarcoma, Melanoma

Hereditary retinoblastoma

25621664, 22355046, 20301625

RECQL

Breast

25915596

RET

Receptor Tyrosine Kinase

Endocrine

Multiple endocrine neoplasia type 2

20301434

NEW RNF43

Serrated polyposis

29330307, 29213343

RPS20

Colon

24941021

SDHB

Succinate dehydrogenase complex

Pheochromocytoma, Paraganglioma

Hereditary paraganglioma-pheochromoctyoma

11404820

SDHC

Succinate dehydrogenase complex

Pheochromocytoma, Paraganglioma

Hereditary paraganglioma-pheochromoctyoma

11062460

SDHD

Succinate dehydrogenase complex

Pheochromocytoma, Paraganglioma

Hereditary paraganglioma-pheochromoctyoma

10657297

SMAD4

TGF-beta signaling

Colon

Juvenile polyposis

20301642

SMARCA4

Ovarian

24658002

TP53

Cell growth

Breast, Ovarian

Li-Fraumeni syndrome

22006311,20301488

TSC1

Hamartomas

Tuberous sclerosis complex

10227394, 9924605, 17287951

TSC2

Hamartomas

Tuberous sclerosis complex

8825048, 9829910

VHL

p53 regulation

Kidney, Neuroendocrine

von Hippel-Lindau syndrome

20301636

*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.

For previous versions of BROCA Cancer Risk Panel, see Previous Versions, BROCA.

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

For providers interested in more information on interpreting genetic test results for your patient, please see the Guide to Interpreting Genomic Reports: A Genomics Toolkit

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.
  2. Under "Check Test Requested," check: "BROCA - Cancer Risk Panel".
  3. For single gene next-generation sequencing or known muatation testing, see Single Gene Analysis [SGN] or Known Mutation Testing [KMU].
  4. To order a subset of genes on the BROCA panel, check: "BROCA - Cancer Risk Panel" and note the genes for which testing is being ordered. Custom BROCA pricing is the same as full BROCA panel.
  5. To order BROCA Paired Tumor, check "BROCA Paired Tumor Panel" and “Normal control”. All BROCA Paired Tumor testing on tumor tissue requires a copy of pathology report to be sent along with the Genetics Requistion form.
  6. To order BROCA on fresh tissue, tumor tissue, cultured fibroblasts, amniocytes, please order BROCA Paired Tumor Panel; a second control sample is not required for germline assessment of normal tissue or cultured cells.
Synonyms
ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BART, BMPR1A, BRCA-negative reflex test, BRCA1, BRCA2, Breast Cancer, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CTNNA1, DICER1, DNA, EPCAM, FANCM, FH, FLCN, GEN1, GREM1, Hereditary Cancer panel, HOXB13, MEN1, MEN2, MET, MITF, MLH1, MLH3, MSH2, MSH3, MSH6, multi-gene panel, MUTYH, NBN, Next-generation sequencing, NF1, NF2, NTHL1, Ovarian Cancer, PALB2, Paraganglioma, Pheochromocytoma, PHOX2B, PIK3CA, PMS2, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RNF43, RPS20, SDHB, SDHC, SDHD, SMAD4, SMARCA4, Succinate dehydrogenase, TP53, TSC1, TSC2, VHL
Components

Interpretation

Method

Next-generation sequencing.

This assay sequences all exons and flanking intronic sequences of ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDK12, CDKN2A, CHEK2, CTNNA1, DICER1, FANCM, FH, FLCN, GEN1, GREM1, HOXB13, MEN1, MET, MITF, MLH1, MLH3, MSH2 (+EPCAM), MSH3, MSH6, MUTYH, NBN, NF1, NF2, NTHL1, PALB2, PHOXB1, PIK3CA, PMS2, POLD1, POLE, POT1, PRKAR1A, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RNF43, 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
Ref. Range Notes

No mutations detected

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

For providers interested in more information on interpreting genetic test results for your patient, please see the Guide to Interpreting Genomic Reports: A Genomics Toolkit

Guidelines

Ordering & Collection

Specimen Type
Peripheral Blood, saliva, or purified DNA from peripheral blood or saliva ONLY. For other sample types, including cultured cells such as fibroblasts or amniocytes, please order BROCA Paired Tumor Panel; BROCOP; paired sample is not required.
Collection

BLOOD:

Preferred: 10 mL whole blood in LAVENDER TOP EDTA tube.
Also acceptable: YELLOW TOP ACD tube, purified DNA from peripheral blood or cultured cells.

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.
  2. Under "Check Test Requested," check: "BROCA - Cancer Risk Panel".
  3. For single gene next-generation sequencing or known muatation testing, see Single Gene Analysis [SGN] or Known Mutation Testing [KMU].
  4. To order a subset of genes on the BROCA panel, check: "BROCA - Cancer Risk Panel" and note the genes for which testing is being ordered. Custom BROCA pricing is the same as full BROCA panel.
  5. To order BROCA Paired Tumor, check "BROCA Paired Tumor Panel" and “Normal control”. All BROCA Paired Tumor testing on tumor tissue requires a copy of pathology report to be sent along with the Genetics Requistion form.
  6. To order BROCA on fresh tissue, tumor tissue, cultured fibroblasts, amniocytes, please order BROCA Paired Tumor Panel; a second control sample is not required for germline assessment of normal tissue or cultured cells.
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: 5 mL whole blood (adult); 2 mL whole blood (pediatric)

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 98195

Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-616-4584
Lab email: cgateam@uw.edu

Tel (EXOME only): 206-543-0459

Faculty
Jillian Buchan, PhD, FACMG
Runjun Kumar, MD, PhD
Regina Kwon, MD, MPH
Christina Lockwood, PhD, DABCC, DABMGG
Brian Shirts, MD, PhD
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: 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.

Genetics Preauthorization Form

LOINC
26435-8
Interfaced Order Code
UOW2684