ColoSeq - Lynch and Polyposis Panel

ColoSeq™ is a comprehensive genetic test for hereditary colon cancer that uses next-generation sequencing to detect most variants in APC*, AXIN2, BMPR1A, CDH1, CHEK2, CTNNA1, EPCAM, GREM1, MLH1*, MLH3, MSH2*, MSH3, MSH6*, MUTYH, NTHL1, PDGFRA, PIK3CA, PMS2*, POLD1, POLE, PTEN, RNF43, RPS20, SMAD4, STK11, and TP53. Mutations in these genes are associated with Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM), familial adenomatous polyposis (APC), MUTYH-associated polyposis, Li- Fraumeni (TP53), Hereditary Diffuse Gastric Cancer (CDH1), Cowden syndrome (PTEN), Peutz-Jeghers syndrome (STK11), Turcot syndrome (APC), PTEN Hamartoma Tumor syndrome (PHTS), Bannayan-Riley-Ruvalcaba syndrome (PTEN), and Juvenile Polyposis syndrome (SMAD4 and BMPR1A). The assay completely sequences all exons, flanking regions of these genes and detects large deletions and duplications. For genes indicated above with *, intronic regions are sequenced. The panel capture detects the MSH2 exon 1-7 inversion (since 2015) described by Rhees, Arnold and Boland 2014. The panel also includes promoter 1B regions of the APC gene including deletions and gastric polyposis causing variants reported in Li et al. 2016.

ColoSeq™ Tumor

Beginning in 2014, ColoSeq™ Tumor is offered for the detection of somatic mutations in tumors. Double 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 et al. 2014, Haraldsdottir et al. 2014). In the absence of a germline MMR mutation, the presence of double somatic mutations in tumor greatly reduces the likelihood that IHC loss of MMR protein(s) is due to an undetected germline mutation, reducing the likelihood the patient has Lynch syndrome.

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) and BRAF V600E status. ColoSeq™ Tumor Single Gene and ColoSeq™ Tumor Panel testing are available. See ColoSeq Tumor Panel [CSQTP] for additional information.

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

ColoSeq™ Panel Genes

Single Gene Testing Available for any Gene on ColoSeq™

For information on single gene testing see BROCA/ColoSeq™ - Single Gene Analysis [SGN]

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 Testing [KMU].

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

• 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
• Li J et al. Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant. Am J Hum Genet 2016 May, 5;98(5):830-842. 27087319
• 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
• Herman DS, et al. Efficient Detection of Copy Number Mutations in PMS2 Exons with a Close Homolog. J Mol Diagn 2018, 20:512-521. 29792936

For providers interested in more information on interpreting genetic test results for your patient, please see the Guide to Interpreting Genomic Reports: A Genomics Toolkit