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BROCA - Cancer Risk Panel

Questions: 1-800-713-5198

Background

BROCA Gene List

GeneFunction/PathwayHeterozygote Cancer risk*Associated syndromeReferences (PMID)
AKT1AKT signalingBreast, ThyroidCowden-like23246288
APCWNT signalingColonFamilial adenomatous polyposis20301519
ATMDouble stranded break repairBreast, PancreaticAtaxia telangiectasia (recessive)16832357,19781682,22585167
ATRDouble stranded break repairOropharyngealSeckel (recessive)22341969
BAP1BRCA1-associated protein complexUveal Melanoma, Mesothelioma21874000,21874003
BARD1BRCA1-associated protein complexBreast, Ovarian21344236
BMPR1ATGF-beta signalingColonJuvenile polyposis20301642
BRCA1BRCA1-associated protein complexBreast, OvarianHereditary breast and ovarian cancer22006311,2270482,7545954
BRCA2Fanconi/BRCABreast, OvarianHereditary breast and ovarian cancer, Fanconi anaemia FA-D1 (recessive)22006311,8524414
BRIP1Fanconi/BRCABreast, OvarianFanconi anaemia FA-J (recessive)22006311,17033622,21964575
CDH1Cell adhesionBreast, GastricHereditary diffuse gastric cancer 20301318
CDK4Cell cycleMelanoma19585149
CDKN2ACell cyclePancreatic, Melanoma19585149
CHEK1Double stranded break repairUnknown11479205
CHEK2Double stranded break repairBreast11967536
CTNNA1Beta-catenin, e-cadherin complexGastricHereditary diffuse gastric cancer23208944
FAM175A/AbraxasDouble stranded break repairBreast22357538
GALNT12O-glycosylationColon19617566,22461326
GEN1Double stranded break repairBreast2052659
GREM1BMP antagonistColonHereditary mixed polyposis syndrome22561515
HOXB13transcription factorProstate22236224
MEN1Gene expression regulationEndocrineMultiple endocrine neoplasia type 19215689
MLH1Mismatch DNA repairColon, Ovarian, EndometrialLynch syndrome20301390
MRE11ADouble stranded break repairBreastAtaxia-telangiectasia-like disorder (recessive)10612394,19383352
MSH2 (+EPCAM)Mismatch DNA repairColon, Ovarian, EndometrialLynch syndrome20301390
MSH6Mismatch DNA repairColon, EndometrialLynch syndrome20301390
MUTYHDNA repairColon (homozygotes)MUTYH-associated polyposis20301519,21952991
NBNDouble stranded break repairBreastNijmegen breakage syndrome (recessive)15185344,9590180
PALB2Fanconi/BRCABreast, PancreaticFanconi anaemia FA-N (recessive)17200668,17200671
PIK3CAAKT signalingBreast, ThyroidCowden-like22729224,23246288
PMS2Mismatch DNA repairColon, EndometrialLynch syndrome20301390
POLD1DNA PolymeraseColon, EndometrialFamilial polyposis, colorectal cancer23263490,23770608
POLEDNA PolymeraseColonFamilial polyposis, colorectal cancer23263490
PRSS1Digestion (Trypsin 1)PancreaticPancreatitis22379635
PTENPI3K/MAPK SignalingBreastCowden syndrome20301661
RAD51BDouble stranded break repairUnknown24139550
RAD51CFanconi/BRCAOvarian, BreastFanconi anaemia FA-O (recessive)22006311,22538716
RAD51DFanconi/BRCAOvarian, BreastFanconi anaemia (recessive)21822267,22415235
RETReceptor Tyrosine KinaseEndocrineMultiple endocrine neoplasia type 220301434
SDHBSuccinate dehydrogenase complexPheochromocytoma, ParagangliomaHereditary paraganglioma-pheochromoctyoma11404820
SDHCSuccinate dehydrogenase complexPheochromocytoma, ParagangliomaHereditary paraganglioma-pheochromoctyoma11062460
SDHDSuccinate dehydrogenase complexPheochromocytoma, ParagangliomaHereditary paraganglioma-pheochromoctyoma10657297
NEW SLX4Fanconi/BRCAUnknownFanconi anaemia (recessive)23840564
SMAD4TGF-beta signalingColonJuvenile polyposis20301642
STK11Cell Cycle/p53 regulationBreast, PancreaticPeutz-Jeghers syndrome20301443
TP53Cell growthBreast, OvarianLi-Fraumeni syndrome22006311,20301488
VHLp53 regulationKidney, Neuroendocrinevon Hippel-Lindau syndrome20301636
XRCC2Double stranded break repairBreastFanconi 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.

Methods

This assay sequences all exons and flanking intronic sequences of AKT1, APC, ATM, ATR, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK1, CHEK2, CTNNA1, FAM175A (Abraxas), GALNT12, GEN1, GREM1, HOXB13, MEN1, MLH1, MRE11A, MSH2 (+EPCAM), MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, POLD1, POLE, PRSS1, PTEN, RAD51B, RAD51C, RAD51D, RET, SDHB, SDHC, SDHD, SLX4, SMAD4, STK11, TP53, VHL, and XRCC2. A total of 1.1 Mb (1.1 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 (1) and 2011 (2). Large deletions and duplications are detected using methods described by Nord et al. 2011 (3).

Requisition Form

  1. Fill out a Clinical Lab Request - Genetics - available at UWMC Genetics Requisition

  2. Under "Check Test Requested," check: "BROCA - Cancer Risk Panel"
  3. 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. For single gene next-generation sequencing, see Single Gene analysis.

Specimen Requirements and Handling

10 mL whole blood in lavender top (EDTA) tube. ACD is also acceptable.

Turnaround Time

8 weeks (56 days)

CPT Codes & Pricing

Billing and Insurance Pre-Authorization

Reference Range

No mutation detected.

Contact Us

For further information:

References

  1. Walsh T, Lee MK, Casadei S, Thornton AM, Stray SM, Pennil C, Nord AS, Mandell JB, Swisher EM, King MC. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. PNAS (2010) 107:12629-33.

  2. Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, Roeb W, Agnew KJ, Stray SM, Wickramanayake A, Norquist B, Pennington KP, Garcia RL, King MC, Swisher EM. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. PNAS (2011) 108:18032-7.

  3. Nord AS, Lee M, King MC, Walsh T. Accurate and exact CNV identification from targeted high-throughput sequence data. BMC Genomics. (2011) 12:184.

  4. Metzker ML. Sequencing technologies - the next generation. Nat Rev Genet. (2010) 11:31-46.C

2014-10-18 16:22