BROCA Paired Tumor Panel

tabbed view

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 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

18724359, 28674118

AKT1

AKT signaling

Breast, Thyroid

Cowden-like

23246288

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

WNT signaling

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

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

20301365

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 cancer, frequently somatic 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

CTNNB1

WNT signaling

Typically somatic only

Colon cancer, endometrial cancer, desmoid tumors, colon adenomas

33115416, 37048063

DICER1

Tumor suppressor

Wilms tumor, pleuropulmonary blastoma

DICER1 syndrome

29343557, 28960912, 23625684

ENG

Transforming growth factor-beta (TGFB) receptor complex and binds TGFB1

Colon polyps, telangiectasia

Hereditary Hemorrahagic Telangiectasia, type 1), potential colon polyposis syndrome

23399955, 16287957

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. Primary spontaneous pneumothorax.

12204536, 19659657

GALNT12

O-glycosylation

Colon

unknown

19617566, 22461326

GEN1

Double stranded break repair

Breast

Hereditary breast cancer

2052659

GREM1

BMP antagonist

Colon

Hereditary mixed polyposis syndrome

22561515

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

24362817, 25335490

MAX

MYC signaling

Pheochromocytoma, Paraganglioma

Hereditary pheochromocytoma and paraganglioma

21685915, 22452945

MBD4

Mismatch DNA repair

Uveal Melanoma, myelodyplastic disease, colon polyposis

Polyposis, multi-organ tumor predisposition (recessive)

32239153, 35460607

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

MLH3

Mismatch DNA repair

Polyposis (recessive)

unknown

30573798

MRE11A

Double stranded break repair

Breast

Ataxia-telangiectasia-like disorder (recessive)

10612394, 19383352

MSH2 (+EPCAM)

Mismatch DNA repair

Colon, Ovarian, Endometrial

Lynch syndrome

20301390

MSH3

Mismatch DNA repair

Polyposis

Familial adenomatous polyposis 4 (recessive)

27476653, 35675019, 38243056

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

PDGFRA

Protein tyrosine kinase

GIST

Familial, sporadic GIST

25975287, 23036227

PHOXB2

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

Melanoma, CLL, Sarcoma, Glioma, Colon, Thyroid, Breast

Multi-organ tumor predisposition

23502782, 24686849, 28853721

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 anaemia (recessive)

21822267, 22415235

RB1

Tumor suppressor

Retinoblastoma, Sarcoma, Melanoma

Hereditary retinoblastoma

25621664, 22355046, 20301625

RECQL

DNA repair

Breast

Hereditary breast cancer

25915596

RET

Receptor Tyrosine Kinase

Endocrine

Multiple endocrine neoplasia type 2

20301434

RINT1

DNA checkpoint regulation

Breast, Colon

Multi-organ tumor predisposition

25050558

RNF43

WNT signaling

Colon

Sessile Serrated Polyposis 27329244, 27081527

RPS20

Ribosomal protein

Colon

unknown

24941021

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

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

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

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

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

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
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 98195

Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-598–0304
Lab email: cgateam@uw.edu

Tel (EXOME only): 206-543-0459

Manager
Joe Bernal

Genetic Counselors
Angela Jacobson, MS, LGC
Sandra Coe, MS,LGC
Dru Leistritz, MS, LGC(EXOME testing only)

Variant Review Scientist
Ankita Jhuraney, PhD
Sarah Paolucci, MA, MS, LGC
Catherine A. Darcey, MSc
Daniel W. Serber, PhD, MS, LCGC

Faculty
Jillian Buchan, PhD, FACMG
Runjun Kumar, MD, PhD
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
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.

Genetics Preauthorization Form

LOINC
47997-2
Interfaced Order Code
UOW3817