Lynch Syndrome

Forms and Documents

Test Details

APC, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2
  • Effective 1/29/2018, MSH2 Inversion Analysis will be included on all Oncology panels with the MSH2 gene.
  • Colorectal or endometrial cancer diagnosed under 50 years of age
  • Multiple colon polyps (especially ≥ 20 adenomas) at any age
  • Tumor testing which indicates an increased risk for a hereditary cancer syndrome known as Lynch syndrome (e.g. microsatellite instability and/or lack of immunohistochemistry staining for a mismatch repair protein)
  • Multiple cancers in one person either of the same origin (such as two separate colorectal cancers) or of different origin (such as colon and endometrial cancer in the same individual)
  • Multiple relatives diagnosed with the same or related cancers (such as colon, endometrial, ovarian, urinary tract, gastric) on the same side of the family and spanning multiple generations
  • Exon Array CGH
  • Next-Gen Sequencing
  • MLPA

Ordering

B522
2 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

81292x1, 81294x1, 81295x1, 81297x1, 81317x1, 81298x1, 81300x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Baglietto L et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010 Feb;102(3):193-201. (PMID: 20028993)
  2. Balaguer F et al. Identification of MYH mutation carriers in colorectal cancer: a multicenter, case-control, population-based study. Clin Gastroenterol Hepatol. 2007;5:379–87. (PMID:17368238)
  3. Barnetson RA et al. Germline mutation prevalence in the base excision repair gene, MYH, in patients with endometrial cancer. Clin Genet. 2007 Dec;72(6):551-5. (PMID: 17956577)
  4. Bonadona V et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011 Jun;305(22):2304-10. (PMID: 21642682)
  5. Bonpari KS et al. Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. Gastroenterology. 2008 Dec;135(6):2014-8. (PMID: 19013464)
  6. Cleary SP et al. Germline MutY human homologue mutations and colorectal cancer: a multisite case-control study. Gastroenterology. 2009;136:1251–60. (PMID:19245865)
  7. Croitoru ME et al. Association Between Biallelic and Monoallelic Germline MYH Gene Mutations and Colorectal Cancer Risk. JNCI. 2004;96:1631–4. (PMID:15523092)
  8. Durno CA et al. The gastrointestinal phenotype of germline biallelic mismatch repair gene mutations. Am J Gastroenterol. 2010 Nov;105(11):2449-56. (PMID:20531397)
  9. Farrington SM et al. Germline susceptibility to colorectal cancer due to base-excision repair gene defects. Am J Hum Genet. 2005;77:112–9. (PMID:15931596)
  10. Jasperson KW et al. Hereditary and Familial Colon Cancer. Gastroenterology. 2010 Jun;138(6):2044-58 (PMID: 20420945)
  11. Jasperson KW. Genetic testing by cancer site: colon (polyposis syndromes). Cancer J. 2012 Jul-Aug;18(4):328-33. (PMID: 22846733)
  12. Jenkins MA et al. Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer Epidemiol Biomarkers Prev. 2006;15:312-14. (PMID: 16492921)
  13. Li-Chang HH et al. Colorectal cancer in a 9-year-old due to combined EPCAM and MSH2 germline mutations: case report of a unique genotype and immunophenotype. J Clin Pathol. 2013 Jul;66(7):631-3. (PMID: 23454724)
  14. Lubbe SJ et al. Clinical implications of the colorectal cancer risk associated with MUTYH mutations. J Clin Oncol. 2009;27:3975-80. (PMID: 19620482)
  15. Out AA et al. MUTYH gene variants and breast cancer in a Dutch case-control study. Breast Cancer Res Treat. 2012 Jul;134(1):219-27. ( PMID:22297469)
  16. Quehenberger F et al. Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment. J Med Genet.2005 Jun;42(6):491-6. (PMID: 21642682)
  17. Rennert G et al. MutYH mutation carriers have increased breast cancer risk. Cancer. 2012 Apr;118(8):1989-93. (PMID: 21952991)
  18. Santonocito C et al. Common genetic variants of MUTYH are not associated with cutaneous malignant melanoma: application of molecular screening by means of high-resolution melting technique in a pilot case-control study. Int J Biol Markers. 2011 Jan-Mar;26
  19. Senter L et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008 Aug;135(2):419-28. (PMID: 18602922)
  20. Sieber OM et al. Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. N Engl J Med. 2003 Feb 27;348(9):791-9. (PMID:12606733)
  21. Vasen HF et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996 Apr;110(4):1020-7. (PMID: 8612988)
  22. Vogt S. et al. Expanded extracolonic tumor spectrum in MUTYH-associated polyposis. Gastroenterology. 2009;137:1976-85. (PMID: 19732775)
  23. Weissman SM et al. Genetic counseling considerations in the evaluation of families for Lynch syndrome--a review.J Genet Couns. 2011 Feb;20(1):5-19. (PMID: 20931355)
  24. Wimmer K et al. Constitutional mismatch repair-deficiency syndrome. Haematologica. 2010 May; 95(5): 699–701. (PMID:20442441)
  25. Win AK et al. Cancer risks for monoallelic MUTYH mutation carriers with a family history of colorectal cancer. Int J Cancer. 2011 Nov 1;129(9):2256-62. (PMID: 21171015)
  26. Win AK et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol. 2012 Mar;30(9):958-64. (PMID: 22331944)

Forms and Documents

Test Details

APC, ATM, AXIN2, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDKN2A, CHEK2, EPCAM, FH, FLCN, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SCG5/GREM1, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL
  • Effective 1/29/2018, MSH2 Inversion Analysis will be included on all Oncology panels with the MSH2 gene.
  • Cancer at a young age, such as breast or colon cancer
  • Multiple cancers in one person, either of the same origin (such as two separate colon cancers) or of different origins (such as breast cancer and ovarian cancer)
  • Diagnosis of certain rare cancers, such as ovarian or male breast cancer
  • Multiple relatives diagnosed with the same or related cancers on the same side of the family and spanning multiple generations
  • Exon Array CGH
  • Next-Gen Sequencing
  • MLPA

Ordering

B751
2 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81162x1, 81201x1, 81203x1, 81292x1, 81294x1, 81295x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Canto MI et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar;62(3):339-47. (PMID 23135763)
  2. National Cancer Institute at the National Institutes of Health. What you need to know about: cancer; risk factors. (URL: http://www.cancer.gov/cancertopics) [July 2013 accessed].
  3. NCCN Guidelines.Gastric Cancer. (URL: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp) [July 2014 accessed].
  4. NCCN Guidelines. Genetic/Familial High-Risk Assessment: Breast and Ovarian. (URL: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp) [May 2013 accessed].
  5. NCCN Guidelines. Genetic/Familial High-Risk Assessment: Colorectal. (URL: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp) [May 2014 accessed].
  6. Saslow D et al. American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography.CA Cancer J Clin. 2007 May-Jun; 57(3):185. (PMID 17392385)
  7. Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. SEER Cancer Statistics Review, 1975-2009: Lifetime Risk Tables (URL: http://surveillance.cancer.gov/devcan) [July 2013 accessed].

Forms and Documents

Test Details

MSH2
  • Effective 1/29/2018, MSH2 Inversion Analysis will be included on all Oncology panels with the MSH2 gene.
  • Identify the genetic basis of cancer for individuals who have features and/or a family history consistent with one of the hereditary cancer syndromes described above. Determine appropriate clinical management recommendations based on a molecular diagnosis.
  • Identify family members at-risk to develop features associated with a specific hereditary cancer syndrome.
  • PCR & Electrophoresis

Ordering

J006
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

N/A
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Baglietto L et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010 Feb;102(3):193-201. (PMID: 20028993)
  2. Bonadona V et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011 Jun;305(22):2304-10. (PMID: 21642682)
  3. Canto M et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut. 2013 Mar;62(3):339-47. (PMID: 23135763)
  4. Cunningham JM et al. The frequency of hereditary defective mismatch repair in a prospective series of unselected colorectal carcinomas. Am J Hum Genet. 2001 Oct;69(4):780-90. (PMID: 11524701)
  5. Durno CA et al. The gastrointestinal phenotype of germline biallelic mismatch repair gene mutations. Am J Gastroenterol. 2010 Nov;105(11):2449-56. (PMID: 20531397)
  6. Li-Chang HH et al. Colorectal cancer in a 9-year-old due to combined EPCAM and MSH2 germline mutations: case report of a unique genotype and immunophenotype. J Clin Pathol. 2013 Jul;66(7):631-3. (PMID: 23454724)
  7. NCCN Guidelines. Genetic/Familial High-Risk Assessment: Colorectal. (URL: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp) [May 2014 accessed].
  8. Quehenberger F et al. Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainment. J Med Genet.2005 Jun;42(6):491-6. (PMID: 21642682)
  9. Rhees J et al. Inversion of exons 1-7 of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population. Fam Cancer. 2014 Jun;13(2):219-25. (PMID: 24114314)
  10. Senter L et al. The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations. Gastroenterology. 2008 Aug;135(2):419-28. (PMID: 18602922)
  11. Vasen HF et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology. 1996 Apr;110(4):1020-7. (PMID: 8612988)
  12. Weissman SM et al. Genetic counseling considerations in the evaluation of families for Lynch syndrome--a review.J Genet Couns. 2011 Feb;20(1):5-19. (PMID: 20931355)
  13. Wimmer K et al. Constitutional mismatch repair-deficiency syndrome. Haematologica. 2010 May; 95(5): 699–701. (PMID: 20442441)

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Effective 1/29/2018, MSH2 Inversion Analysis will be included on all Oncology panels with the MSH2 gene.
  • Identify the genetic basis of cancer for individuals who have features and/or a family history consistent with one of the hereditary cancer syndromes described above.
  • Determine appropriate clinical management recommendations based on a molecular diagnosis.
  • Identify family members at-risk to develop features associated with a specific hereditary cancer syndrome.
  • Exon Array CGH
  • Next-Gen Sequencing
  • MLPA

Ordering

B749
21 days
2-5 mL Blood - Lavender Top Tube
Buccal Swab | Fibroblasts (separate charge for cell culture may apply) | Oral Rinse

Billing

Varies by Gene
Yes
Yes
* For price inquiries please email zebras@genedx.com