BROCA Cancer Risk Panel

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General Information

Lab Name
BROCA Cancer Risk Panel
Lab Code
BROCA
ORCA Name
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 mutations in ALK, AKT1, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK1, CHEK2, CTNNA1, EPCAM, FAM175A, FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, KIF1B, MEN1, MET, MITF, MLH1, MRE11A, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PALLD, PDGFRA, PHOX2B, PIK3CA, PMS2, POLD1, POLE, POT1, PRKAR1A, PRSS1, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SLX4, SMAD4, SMARCA4, TP53, VHL, and XRCC2. The assay completely sequences all exons of these genes AND detects large deletions and duplications.

  • BROCA is useful for the 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).
  • The test uses next-generation sequencing to detect mutations in the genes listed in the table below. The assay completely sequences all exons, non repeating introns, and select promoter regions of these genes AND detects large deletions, duplications, and mosaicism.
  • 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 via testing at the UW Genetics Laboratory.
  • Custom BROCA can be ordered by specifying genes for which testing is requested on the Genetics Requisition; pricing is the same as full BROCA Cancer Risk Panel.
  • For Ashkenazi Jewish patients, testing for the three BRCA1/2 founder mutations is available, see BRCA1&2 Ashkenazi Mutations [BRCAAJ].
  • For patients with a suspected hereditary colon cancer syndrome, see ColoSeq - Lynch and Polyposis Panel [COSEQ].

BROCA Gene List

Gene Function/Pathway Heterozygote Cancer risk* Associated syndrome References (PMID)
NEW ALK MYC signaling Neuroblastoma 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 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
CDKN2A Cell cycle Pancreatic, Melanoma 19585149
CHEK1 Double stranded break repair Unknown 11479205
CHEK2 Double stranded break repair Breast 11967536
CTNNA1 Beta-catenin, e-cadherin complex Gastric Hereditary diffuse gastric cancer 23208944
FAM175A/Abraxas Double stranded break repair Breast 22357538
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
GALNT12 O-glycosylation Colon 19617566,22461326
GEN1 Double stranded break repair Breast 2052659
GREM1 BMP antagonist Colon Hereditary mixed polyposis syndrome 22561515
HOXB13 transcription factor Prostate 22236224
NEW KIF1B Neuroblastoma 18726616,18334619
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
MRE11A Double stranded break repair Breast Ataxia-telangiectasia-like disorder (recessive) 10612394,19383352
MSH2 (+EPCAM) Mismatch DNA repair Colon, Ovarian, Endometrial Lynch syndrome 20301390
NEW 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
NTHL1 Colon Polyposis (recessive) 25938944,26431160
PALB2 Fanconi/BRCA Breast, Pancreatic Fanconi anaemia FA-N (recessive) 17200668,17200671,25099575
PALLD Pancreatic Familial pancreatic cancer 17194196
PDGFRA GIST 25975287,23036227
NEW 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
PRSS1 Digestion (Trypsin 1) Pancreatic Pancreatitis 22379635
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 Fanconi anaemia (recessive) 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
RINT1 Breast, Colon 25050558
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
SLX4 Fanconi/BRCA Unknown Fanconi anaemia (recessive) 23840564
SMAD4 TGF-beta signaling Colon Juvenile polyposis 20301642
SMARCA4 Ovarian 24658002
TP53 Cell growth Breast, Ovarian Li-Fraumeni syndrome 22006311,20301488
VHL p53 regulation Kidney, Neuroendocrine von Hippel-Lindau syndrome 20301636
XRCC2 Double stranded break repair Breast Fanconi anaemia (recessive) 22464251,22232082

*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
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 panel germline testing with paired tumor control, check "BROCA - Cancer Risk Panel" and indicate tumor control is desired in the clinical history field. All BROCA panel testing with tumor control require a copy of pathology report to be sent along with the Genetics Requistion form.
Synonyms
AKT1, ALK, APC, ATM, ATR, AXIN2, BAP1, BARD1, BART, BMPR1A, BRCA-negative reflex test, BRCA1, BRCA2, BRIP1, Breast Cancer, CDH1, CDK4, CDKN2A, CHEK1, CHEK2, CTNNA1, DNA, EPCAM, FAM175A, FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, Hereditary Cancer panel, KIF1B, MEN1, MEN2, MET, MITF, MLH1, MRE11A, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, Next-generation sequencing, Ovarian Cancer, PALB2, PALLD, PDGFRA, PHOX2B, PIK3CA, PMS2, POLD1, POLE, POT1, PRKAR1A, PRSS1, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SLX4, SMAD4, SMARCA4, TP53, VHL, XRCC2, multi-gene panel
Components

Interpretation

Method

Next-generation sequencing.

This assay sequences all exons and flanking intronic sequences of ALK, AKT1, APC, ATM, ATR, AXIN2, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK1, CHEK2, CTNNA1, FAM175A (Abraxas), FANCM, FH, FLCN, GALNT12, GEN1, GREM1, HOXB13, KIF1B, MEN1, MET, MITF, MLH1, MRE11A, MSH2 (+EPCAM), MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PALLD, PDGFRA, PHOXB1, PIK3CA, PMS2, POLD1, POLE, POT1, PRKAR1A, PRSS1, PTCH1, PTEN, RAD51B, RAD51C, RAD51D, RB1, RECQL, RET, RINT1, RPS20, SDHB, SDHC, SDHD, SLX4, SMAD4, SMARCA4, TP53, VHL, and XRCC2. A total of 1.4 Mb (1.4 Million base pairs) are sequenced and the average coverage ranges from 320 to >1,000 sequencing reads per bp. Genomic regions are captured using biotinylated RNA oliognucleotides (SureSelect), prepared in paired-end libraries with ~200 bp insert size, and sequenced on an Illumina HiSeq2000 instrument with 100 bp read lengths, in a modification of a procedure described by Walsh et al. 2010 and 2011. Large deletions and duplications are detected using methods described by Nord et al. 2011.

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

Ordering & Collection

Specimen Type
Peripheral Blood, cultured cells from skin biopsy, purified DNA from peripheral blood or cultured cells
Collection

BLOOD:

  • 10 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)*.

*Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide [[MCC]] for ordering and specimen requirements)

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 panel germline testing with paired tumor control, check "BROCA - Cancer Risk Panel" and indicate tumor control is desired in the clinical history field. All BROCA panel testing with tumor control require a copy of pathology report to be sent along with the Genetics Requistion form.
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

Processing

Processing

Blood: Refrigerate whole blood

Unacceptable Conditions: Frozen or clotted specimens

Stability (collection to initiation of testing): Ambient: 24 hr; Refrigerated: 5 days; Frozen: Unacceptable

Purified DNA: Refrigerate DNA specimens. Frozen is acceptable.

Performance

LIS Dept Code
Genetics (GEN)
Performing Location(s)
UWMC 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: genelab@uw.edu

Supervisor

Robert Livingston, PhD bobl@uw.edu

Genetic Counselors

Angela Jacobson, MS, LGC agibson@uw.edu
Ginger Tsai, MS, LGC, gjtsai@uw.edu

Faculty

Colin C. Pritchard, MD, PhD
Brian H. Shirts, MD, PhD
Christina Lockwood, PhD, DABCC
Stephen Salipante, MD, PhD
Eric Konnick, MD, MS
Karen Stephens, PhD, FACMG
Jonathan F. Tait, MD, PhD
Vera Paulson, MD, PhD

Frequency
Results within 4-6 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: ngsbill@uw.edu or call 1-855-320-4869 for more information.

Genetics Preauthorization Form

LOINC
26435-8