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ColoSeq™ and ColoSeq™ Tumor - Lynch and Polyposis Panel

Questions: 1-800-713-5198

Background

ColoSeq - Lynch and Polyposis Gene Panel

ColoSeq™ is a comprehensive genetic test for hereditary colon cancer that uses next-generation sequencing to detect mutations in multiple genes associated with Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC), familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), hereditary diffuse gastric cancer (HDGC), Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, Muir-Torre syndrome, Turcot syndrome, and Juvenile Polyposis syndrome. The assay sequences all exons, introns, and flanking sequences of the 22 genes listed in the table below. Large deletions, duplications, and mosaicism are also detected by the assay and reported. AXIN2 and RPS20 were added to the panel in February 2015, and the panel capture now detects the MSH2 exon 1-7 inversion recently described by Rhees J, Arnold M and Boland CR (2014). There is no change to pricing, ordering or specimen requirements with the update.

Patient information on next-generation sequencing, Points to Consider, is available. For information about how University of Washington Department of Laboratory Medicine reports variants, see Variant Policy.

Introducing ColoSeq™ Tumor

Beginning in 2014, ColoSeq™ Tumor is offered for detection of somatic mutations in tumors. Somatic mismatch repair (MMR) mutations have been reported in colon and endometrial cancers which have IHC loss of MMR protein(s) and normal (negative) germline MMR testing (Mensenkamp 2014, Haraldsdottir 2014). ColoSeq™ Tumor is an option for patients who have had abnormal MMR IHC and normal germline testing, such as ColoSeq™. ColoSeq™ Tumor can also assess microsatellite instability in colon cancer (Salipante 2014). Single gene testing can also be ordered on tumor. See below for specimen requirements and ordering instructions. NOTE: If germline MMR testing was performed in a different laboratory, a peripheral blood sample should be submitted in addition to tumor tissue.

ColoSeq™ Panel Genes

Gene

RefSeq

Disease Association or Cancer Risk

Complete Sequencing

Del/Dup

Added

MLH1

NM_000249.3

Lynch, Muir-Torre

Yes

Yes

November 2011

MSH2, includes exon 1-7 inversion

NM_000251.1

Lynch, Muir-Torre

Yes

Yes

November 2011

MSH6

NM_000179.2

Lynch

Yes

Yes

November 2011

PMS2

NM_000535.5

Lynch

Yes

Yes

November 2011

EPCAM

NM_002354.2

Lynch

Yes

Yes

November 2011

APC

NM_000038.5

FAP, Turcot

Yes

Yes

November 2011

MUTYH

NM_001128425.1

MUTYH-associated polyposis

Yes

Yes

November 2011

CDH1

NM_004360.3

Hereditary diffuse gastric cancer

Yes

Yes

June 2012

CTNNA1

NM_0011903.2

Hereditary diffuse gastric cancer

Yes

Yes

October 2014

PTEN

NM_000314.4

Cowden

Yes

Yes

June 2012

AKT1

NM_005163.2

Cowden-like, Breast, thyroid cancers, macrocephaly

Yes

Yes

October 2013

PIK3CA

NM_006218.2

Cowden-like, Breast, thyroid cancer, macrocephaly

Yes

Yes

October 2013

STK11

NM_000455.4

Peutz-Jeghers

Yes

Yes

June 2012

TP53

NM_000546.5

Li-Fraumeni

Yes

Yes

June 2012

CHEK2

NM_007194.3

Li-Fraumeni-like

Yes

Yes

February 2015

SMAD4

NM_005359.5

Juvenile Polyposis

Yes

YES

January 2013

BMPR1A

NM_004329.2

Juvenile Polyposis

Yes

Yes

January 2013

POLE

NM_006231.2

Colon cancer

Yes

Yes

October 2013

POLD1

NM_002691.3

Colon cancer

Yes

Yes

October 2013

GALNT12

NM_024642.4

Colon cancer

Yes

Yes

October 2013

GREM1

NM_001191323.1

Polyposis

Yes

Yes

October 2013

AXIN2

NM_004655.3

Colon cancer, oligodontia

Yes

Yes

February 2015

RPS20

NM_001023.3

Colon cancer

Yes

Yes

February 2015

Single Gene Testing available for any gene on ColoSeq™

For information on single gene testing see BROCA/ColoSeq - Single Gene

Known Mutation Testing

Known mutation testing is available for mutations identified at UW Laboratory Medicine. For information on single site testing of a known mutation in one of the genes listed above see BROCA/ColoSeq - Known Mutation

Methods

This assay sequences all exons, non repeating intronic sequences and select promoter regions of AKT1, APC, AXIN2, BMPR1A, CDH1, CTNNA1, EPCAM, GALNT12, GREM1, MLH1, MSH2, MSH6, MUTYH, PIK3CA, PMS2, POLE, POLD1, PTEN, RPS20, SMAD4, STK11, and TP53. A total of 445Kb 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 Pritchard et al. 2012 (1). Large deletions and duplications are detected using methods described by Nord et al. 2011 (2). For previous assay versions see Previous Versions.

Requisition Form and Ordering Instructions

Complete UWMC Genetics Requisition.

For ColoSeq™:

  1. In “Next Generation Sequencing" section of test requisition, check: "ColoSeq™ – Lynch and Polyposis Panel"

For ColoSeq™ Tumor:

  1. In “Next Generation Sequencing" section of test requisition, check: "ColoSeq™ – Tumor Panel" or "ColoSeq™ - Tumor Single Gene". For ColoSeq™ - Tumor Single Gene, specify gene in space provided for pedigree and clinical History.

  2. In “Specimen Submitted" section of the test requisition, check "Tissue, fixed block" or "Tissue, fixed slides".
  3. If prior germline MMR testing was done at another laboratory, peripheral blood sample should be also be submitted. In "Next Generation Sequencing" section of test requisition, check "Normal Control (blood)". It is okay to submit tumor tissue/slides separately from control specimen.

Sample Requirements and Specimen Handling

ColoSeq™ germline testing: 10mL whole blood in lavender top (EDTA) tube. ACD is also acceptable.

ColoSeq™ Tumor Panel or Tumor Single Gene: Tissue samples (FFPE) either (a) slides (PREFERRED), OR (b) tissue block

Ship specimens to:

For additional details regarding specimen collection, handling and transport, see the Laboratory Medicine Online Test Guide for COSEQ

CPT Codes and Pricing

Billing and Insurance Pre-Authorization

Turnaround Time

8 weeks (56 days)

Reference Range

No mutation detected.

Contact Us

For further information:

References

  1. Pritchard CC, Smith C, Salipante SJ, Lee MK, Thornton AM, Nord AS, Gulden C, Kupfer SS, Swisher EM, Bennett RL, Novetsky AP, Jarvik GP, Olopade OI, Goodfellow PJ, King MC, Tait JF, Walsh T. ColoSeq Provides Comprehensive Lynch and Polyposis Syndrome Mutational Analysis Using Massively Parallel Sequencing. J Mol Diagn. (2012)14:357-66. PubMed

  2. 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.

  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.

  5. Rhees J, Arnold M, Boland CR. Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population. Fam Cancer (2014) 13:219-225.

  6. Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, Kwint MP, Hoogerbrugge N, Nagtegaal ID, Ligtenberg MJ. Somatic mutations in MLH1 and MSH2 are frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology (2014)146: 643-6.

  7. Haraldsdottir S, Hampel H, Tomsic J, Frankel WL, Pearlman R, de la Chapelle A, Pritchard CC. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology (2014).

  8. Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clinical Chemistry (2014) 60:1192-9.

2015-05-13 07:21