ColoSeq Tumor Panel

tabbed view

General Information

Lab Name
ColoSeq Tumor Panel
Lab Code
CSQTP
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

ColoSeq™ Tumor Panel is designed to detect somatic mutations in the genes on the ColoSeq™ Panel, with specific focus on identifying mutations in the mismatch repair genes. 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.

ColoSeq™ Tumor Panel is an option for patients who have had abnormal MMR IHC but normal germline testing, such as ColoSeq™.

ColoSeq™ Tumor Panel is an assay for tumor samples that detects mutations in the genes included in this panel. MSI testing and BRAF codon 600 testing are included in the panel for colon cancer. Next-generation sequencing is performed on an Illumina instrument to detect single nucleotide variants, insertions, deletions, gene amplifications, and selected translocations.

NOTE: a peripheral blood control sample is needed in addition to tumor tissue if germline ColoSeq™ testing was not performed previously in this laboratory.

ColoSeq Tumor Single Gene [CSQTS] is also available for the analysis of single gene(s) from the ColoSeq™ Tumor Panel.

For information on germline ColoSeq™ Lynch and Polyposis Panel (comprehensive colon cancer risk panel) see, ColoSeq - Lynch and Polyposis Panel [COSEQ]

ColoSeq™ Panel Genes

Gene

Function/Pathway

Heterozygote Cancer Risk*

Associated disease/syndrome

References

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

AXIN2

WNT signaling Colon

Colon cancer, oligodontia

15042511

BAPI

BRCA1-associated protein complex Uveal Melanoma, Mesothelioma

BAP1 Tumor predisposition syndrome

21874000, 21874003

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

CDH1

Cell adhesion Breast, Gastric

Hereditary diffuse gastric cancer

20301318

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

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

GALNT12

O-glycosylation Colon

unknown

19617566, 22461326

GREM1

BMP antagonist Colon

Hereditary mixed polyposis syndrome

22561515

MBD4

Mismatch DNA repair Uveal Melanoma, myelodyplastic disease, colon polyposis

Polyposis, multi-organ tumor predisposition (recessive)

32239153, 35460607, 30049810

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

MUTYH-associated polyposis (recessive)

20301519, 21952991

NTHL1

Base excision repair Colon polyps, Endometrial, Breast, Pancreatic

Hereditary cancer with colon polyposis (recessive)

25938944, 26431160

PDGFRA

Protein tyrosine kinase GIST, often somatic

Familial, sporadic GIST

25975287, 23036227

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, 37140166

PTCH1

Hedgehog Basal cell carcinoma, PNET

Nevoid basal cell-carcinoma syndrome

8681379, 8658145, 20301330

PTEN

PI3K/MAPK Signaling Breast

Cowden syndrome

20301661

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

SMAD4

TGF-beta signaling Colon

Juvenile Polyposis

20301642

TP53

Cell growth Breast, Ovarian

Li-Fraumeni syndrome

22006311, 20301488

For previous versions of ColoSeq™ - Lynch and Polyposis Panel, see Previous Versions, COSEQ.

References
  • Pritchard CC, et al. ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing. J Mol Diagn 2012, 14:357-66. 22658618
  • 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
  • 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
  • Rhees J, Arnold M, and 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, 13:219-25. 24114314
  • Mensenkamp AR, et al. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology 2014, 146:643-646.e8. 24333619
  • Haraldsdottir S, et al. Colon and endometrial cancers with mismatch repair deficiency can arise from somatic, rather than germline, mutations. Gastroenterology 2014, 147:1308-1316.e1. 25194673
  • Salipante SJ, Scroggins SM, Hampel HL, Turner EH, and Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem 2014, 60:1192-9. 24987110
Synonyms
AKT1, APC, ATM, AXIN2, BAP1, biallelic somatic, BMPR1A, BRAF, CDH1, CHEK2, ColoSeq, COSEQ, CTNNA1, CTNNB1, double somatic, ENG, EPCAM, GALNT12, GREM1, hereditary nonpolyposis colorectal cancer, HNPCC, Lynch syndrome, MBD4, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NTHL1, PDGFRA, PIK3CA, PMS2, POLD1, POLE, POT1, PTEN, RNF43, RPS20, RSPO3, SMAD4, TP53
Components

Interpretation

Method

Next-generation sequencing.

This assay sequences all exons, flanking intronic splice site sequences, and select promoter regions of AKT1, APC, ATM, AXIN2, BAP1, BMPR1A, BRAF, CDH1, CHEK2, CTNNA1, CTNNB1, ENG, EPCAM, GALNT12, GREM1, MBD4, MLH1*, MLH3, MSH2*, MSH3, MSH6*, MUTYH, NTHL1, PDGFRA, PIK3CA, PMS2, POLD1, POLE, POT1, PTEN, RNF43, RPS20, RSPO3, SMAD4, TP53. 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
Ref. Range Notes

No mutations detected.

Guidelines

Ordering & Collection

Specimen Type
Formalin-Fixed Paraffin Embedded Tumor Tissue (FFPE), Purified DNA, Peripheral Blood, cultured cells from skin biopsy, purified DNA from peripheral blood or cultured cells, saliva
Collection

Tumor specimen will be requested directly, by UW Laboratory Medicine, 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.

NOTE: This test requires BOTH tumor tissue and peripheral blood. Only tumor tissue is required if ColoSeq™ testing on peripheral blood has been done previously at UW Lab Medicine.

Tumor Tissue:

Tumor specimen will be requested directly, by UW Laboratory Medicine, 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.

NOTE: If germline MMR testing was performed in a different laboratory, a peripheral blood sample should be submitted in addition to tumor tissue.

Germline control sample:

BLOOD:

  • 10 mL whole blood in LAVENDER TOP EDTA tube.
  • Also acceptable: YELLOW TOP ACD tube, purified DNA from peripheral blood or cultured cells.

SALIVA:
Contact laboratory for validated collection kit.

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).
Forms & Requisitions

Requisition Form and Ordering Instructions:

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 (internal link).

2. Check "ColoSeq™ – Tumor Panel" or "ColoSeq™ - Tumor Single Gene" as desired.

3. For ColoSeq™ - Tumor Single Gene, specify gene in space provided.

4. Unless prior germline testing was performed at University of Washington, also select: "Normal Control (blood)."

5. Select the appropriate “Specimen Submitted."

6. Submit test requisition with peripheral blood sample and a copy of the tumor pathology report.

NOTE: Tumor specimen will be requested directly, by UW Laboratory Medicine and Pathology, from the originating pathology department, and therefore, in most cases, it is not necessary to submit tumor block or slides.

Handling Instructions

Attach a copy of the pathology report for the tumor sample being submitted.

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: Tissue: 10 unstained slides plus one H&E-stained; slide or extracted DNA: 5 microgram AND 5 mL control peripheral blood (DNAPRP)

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: 206-616-4584
Lab email: cgateam@uw.edu

Tel (EXOME only): 206-543-0459

Faculty
Jillian Buchan, PhD, FACMG
Runjun Kumar, MD, PhD
Regina Kwon, MD, MPH
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 4-6 weeks, once sample arrives in the laboratory.
Available STAT?
No

Billing & Coding

CPT codes
Billing Comments

For additional test/billing information, see ColoSeq™ Tumor CPT codes.

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.

A letter of medical necessity is highly recommended for ColoSeq™ Tumor testing, and a template is available by emailing genelab@uw.edu.

Genetics Preauthorization Form

LOINC
51967-8
Interfaced Order Code
UOW2961