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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 20 genes listed in the table below. Large deletions, duplications, and mosaicism are also detected by the assay and reported. CTNNA1 was added to the panel in October 2014, 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

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 (NEW)

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

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

ColoSeq - Polyposis Panel (APC and MUTYH only)

For information on ColoSeq™ Polyposis see ColoSeq - Polyposis Panel

BROCA/ColoSeq - Single Gene (Pick One Gene To Test)

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

BROCA/ColoSeq - Known Mutation (Single-Site Testing)

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 and flanking intronic sequences of MLH1, MSH2, MSH6, PMS2, EPCAM, APC, MUTYH, CDH1, CTNNA1, PTEN, AKT1, PIK3CA, STK11, TP53, SMAD4, BMPR1A, POLE, POLD1, GALNT12, and GREM1. 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).

Requisition Form and Ordering Instructions

Complete UWMC Genetics Requisition.

For ColoSeq™:

  1. Under “Check Test Requested,” check: "ColoSeq™ – Lynch and Polyposis Panel"

For ColoSeq™ Tumor:

  1. Under “Check Test Requested,” check: "ColoSeq™ – Lynch and Polyposis Panel"

  2. Under "Specimen Submitted", 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. Under "Tumor/Somatic", check "Normal Control (blood)".

For Single Gene Tumor:

  1. Under "Check Test Requested," check: "Single Gene Analysis (specify gene)".
  2. Under "Specimen Submitted", 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. Under "Tumor/Somatic", check "Normal Control (blood)".

Sample Requirements and Specimen Handling

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

ColoSeq™ or Single Gene Tumor: 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.

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