Laboratory Test Guide

BROCA Cancer Risk Panel

General Information

Lab Name

Lab Code

BROCA

Epic Name

BROCA Cancer Risk Panel

Description

BROCA Cancer Risk panel is useful for the germline (only) evaluation of patients with a suspected hereditary cancer predisposition. 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 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, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, TP53, TSC1, TSC2, and VHL. The assay completely sequences all exons of these genes AND detects large deletions and duplications.

The test uses next-generation sequencing to detect pathogenic variants in the genes listed in the table below. The assay completely sequences exons and flanking intronic sequences of all the genes on the panel, and promotor regions of select genes. The assay detects single nucleotide variants, small insertions, and deletions (indels), large deletions, duplications, and constitutional mosaicism. For genes indicated with *above, full 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.
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.
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.

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	BAP1 Tumor predisposition syndrome	21874000, 21874003
BARD1	BRCA1-associated protein complex	Breast, Ovarian	Hereditary breast cancer	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	Familial melanoma	19585149
CDK12	MAP kinase regulation	Breast, Ovarian	Typically somatic only; Hereditary breast and ovarian cancer	24554720, 29906450, 24240700
CDKN2A	Cell cycle	Pancreatic, Melanoma	Familial melanoma and pancreatic cancer	19585149
CHEK2	Double stranded break repair	Breast	Hereditary breast cancer	11967536
CTNNA1	Beta-catenin, e-cadherin complex	Gastric	Hereditary diffuse gastric cancer	23208944
DICER1	Tumor suppressor	Wilms tumor, pleuropulmonary blastoma	DICER1 syndrome	29343557, 28960912, 23625684
FANCM	Fanconi/BRCA	Breast	Fanconi anemia (recessive)	25288723
FH	Tumor suppressor	Renal	Hereditary leiomyomatosis and renal cell cancer	25018647, 11865300, 25004247
FLCN	Tumor suppressor	Renal	Birt-Hogg-Dube syndrome	12204536, 20301695
GEN1	Double stranded break repair	Breast	Breast	2052659
GREM1	BMP antagonist	Colon	Hereditary mixed polyposis syndrome	22561515
HOXB13	transcription factor	Prostate	Familial prostate cancer	22236224
MEN1	Gene expression regulation	Endocrine	Multiple endocrine neoplasia type 1	9215689
MET	Tyrosine Kinase receptor	Kidney, Squamous cell carcinomas	Hereditary papillary renal cell carcinoma	11551094, 9140397, 27330189
MITF	Melanocyte inducing transcription factor	Kidney, Melanoma	MITF-related melanoma and renal cell carcinoma predisposition	24290354, 22012259
MLH1	Mismatch DNA repair	Colon, Ovarian, Endometrial	Lynch syndrome	20301390
NEW MLH3	Mismatch DNA repair	Polyposis (recessive)	Unknown (recessive)	30573798
MSH2 / EPCAM	Mismatch DNA repair	Colon, Ovarian, Endometrial	Lynch syndrome	20301390
MSH3	Mismatch DNA repair	Polyposis (recessive)	Familial adenomatous polyposis 4 (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	MAPK signaling	Optic Glioma, Peripheral Nerve Sheath, Breast	Neurofibromatosis	2114220, 23165953, 20301288
NF2	Cellular regulation	Acoustic neuromas, Vestibular Schwannomas	Neurofibromatosis 2	20301380
NTHL1	Base excision repair	Colon	Polyposis (recessive)	25938944, 26431160
PALB2	Fanconi/BRCA	Breast, Pancreatic	Fanconi anaemia FA-N (recessive)	17200668, 17200671, 25099575
PHOX2B	Tumor suppressor	Neuroblastoma	Hereditary 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	Telomere maintenance	Brain, Melanoma	Familial melanoma and brain cancer	25482530, 24686849
PRKAR1A	cAMP signaling	Endocrine	Carney complex (recessive)	4010501
PTCH1	Hedgehog	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	Hereditary breast and ovarian cancer	24139550
RAD51C	Fanconi/BRCA	Ovarian, Breast	Fanconi anaemia FA-O (recessive)	22006311, 22538716
RAD51D	Fanconi/BRCA	Ovarian, Breast	Fanconi anemia (recessive)
RB1	Tumor suppressor	Retinoblastoma, Sarcoma, Melanoma	Hereditary retinoblastoma	25621664, 22355046, 20301625
RECQL	DNA repair	Breast	Hereditary retinoblastoma	25915596
RET	Receptor Tyrosine Kinase	Endocrine	Multiple endocrine neoplasia type 2	20301434
NEW RNF43	WNT signaling	Serrated polyposis	Sessile Serrated Polyposis	29330307, 29213343
RPS20	Ribosomal protein	Colon	unknown	24941021
SDHA	Succinate dehydrogenase complex	Pheochromocytoma, Paraganglioma	Hereditary paraganglioma-pheochromoctyoma	20484225, 21752896
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	SWI/SNF complex	Ovarian	Hereditary small cell carcinoma of the ovary, hypercalcemic	24658002
STK11	Tumor suppresso	Breast, Pancreas, Other cancers	Peutz-Jeghers syndrome	20301443
TP53	Cell growth	Breast, Ovarian	Li-Fraumeni syndrome	22006311,20301488
TSC1	Cell growth	Hamartomas	Tuberous sclerosis complex	10227394, 9924605, 17287951
TSC2	Cell growth	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

Synonyms

ALK, and VHL., APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1*, BRCA2*, Breast Cancer, BRIP1, CDH1, CDK12, CDK4, CDKN2A, CHEK2, CTNNA1, DICER1, EPCAM, FANCM, FH, FLCN, GEN1, GREM1, Hereditary Cancer panel, HOXB13, MEN1, 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, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, Succinate dehydrogenase, TP53, TSC1, TSC2

Components

Code	Name
BROCGS	BROCA Genes Sequenced
BROCRE	BROCA Result
BROCIN	BROCA Interpretation
BROCCH	BROCA Clinical History
BROCMT	BROCA Method
BROCDI	BROCA Director

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, 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, SDHA, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, 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

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).

Fill out a Genetics Requisition form.
Under "Check Test Requested," check: "BROCA - Cancer Risk Panel".
For single gene next-generation sequencing or known muatation testing, see Single Gene Analysis [SGN] or Known Mutation Testing [KMU].
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.
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.
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

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 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?

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.

Genetics Preauthorization Form

LOINC

26435-8

Interfaced Order Code

UOW2684