MUTYH-associated Polypsis (MAP)
Familial Adenomatous Polyposis (FAP) is a colon cancer predisposition syndrome characterized by hundreds to thousands of adenomatous polyps in the internal lining of the colon and the rectum.
PrintFamilial Adenomatous Polyposis (FAP) is a colon cancer predisposition syndrome characterized by hundreds to thousands of adenomatous polyps in the internal lining of the colon and the rectum.
The autosomal dominant form of this syndrome, along with its variants Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP) are associated with mutations of the APC gene. A subset of polyposis patients have been demonstrated to carry inherited mutations in the MUTYH gene and have an autosomal recessive form of adenomatous polyposis, known as MUTYH-associated polyposis (MAP). MAP is an autosomal recessive disorder whose clinical manifestations resemble those for FAP and AFAP. Two common mutations, Y179C and G396D (originally designated as Y165C and G382D), have been reported as homozygous or compound heterozygous in about 70%-86% of MAP patients. Therefore, if an APC mutation is not identified in an individual with colonic polyposis, genetic testing of MUTYH should be considered.
The Ambry Test: MUTYH-associated Polyposis (MAP) is a comprehensive, two-step reflexive test option, capable of detecting approximately 99% of described mutations in the MUTYH gene. First, specific mutation analysis (SMA) of Y179C and G396D, two most common mutations in the MUTYH gene, is performed. A reflexive gene sequence analysis of MUTYH will be performed if only one MUTYH mutation is identified in the first step.
Familial adenomatous polyposis (FAP) is an autosomal dominant colon cancer predisposition syndrome characterized by hundreds to thousands of adenomatous polyps in the internal lining of the colon and the rectum. It affects 1/8,000 to 1/10,000 individuals and accounts for about 1% of all colorectal cancers.1 In individuals affected with FAP, colonic polyps generally begin developing at an average age of 15 years.2 Colon cancer is inevitable without colectomy, and the mean age of colon cancer diagnosis in untreated individuals is age 35-40 years.3 Variants of FAP include Gardner syndrome, Turcot syndrome, and attenuated FAP (AFAP). FAP and its variants are associated with mutations of the APC gene.
A subset of polyposis patients has been demonstrated to carry inherited mutations in the MUTYH gene, known as MUTYH-associated polyposis (MAP). MAP is an autosomal recessive disorder whose clinical manifestations resemble those for FAP and AFAP. If an APC mutation is not identified in an individual with colonic adenomatous polyposis, genetic testing of MUTYH should be considered.11 Two common mutations, Y179C and G396D (originally designated as Y165C and G382D), have been reported as homozygous or compound heterozygous in about 70%-86% of MAP patients.12,13 Clinical studies have shown that MUTYH mutations were detected in 33% and 57% of FAP and AFAP patients, respectively, who are negative for mutations in the APC gene.14 Consequently, mutations in the APC and MUTYH mutations are associated with 70-80% of classic FAP cases and 30-40% of AFAP cases.1
Genetic analysis of MUTYH can provide confirmation of a clinical diagnosis of MUTYH-associated Polyposis (MAP). Once the causative mutations have been identified in a patient, testing of other family members can help identify carriers before clinical manifestations are present. Early identification of at-risk family members guides surveillance measures.
This Ambry Test: MUTYH-associated Polyposis is a laboratory-developed test that detects mutations in the MUTYH gene, and it consists of two steps. First, specific mutation analysis (SMA) of Y179C and G396D, two most common mutations in the MUTYH gene, is performed. A reflexive gene sequence analysis of MUTYH will be performed if only one MUTYH mutation is identified in the first step. Specific mutation analysis for individual MUTYH mutations known to be in the family is also available.
MUTYH mutations could be detected in about 33% and 57% of FAP patients and AFAP patients who are negative for mutations in the APC gene, respectively .14 The Ambry Test: MUTYH-associated polyposis (MAP) is capable of detecting approximately 99% of described mutations in MUTYH.
Blood: Collect 3-5 cc from adult or 2 cc minimum from child into EDTA purple-top tube (first choice) or ACD yellow-top tube (second choice). Store at room temperature or refrigerate. Ship at room temperature.
Blood Spot: Call for availability.
Saliva: Collect 2 ml into Oragene™ DNA Self-Collection container. Store and ship at room temperature.
DNA: Send 20 µg in TE at 50-100 ng/µl. Store frozen and ship on ice or dry ice.
Testing Under 18 years of Age: Please call an Ambry Genetic Counselor to discuss your case.
| Test Code | Technique | CPT Codes |
|---|---|---|
| 4660 | MUTYH Gene Sequence Analysis | 83891x1, 83894x11, 83898x10, 83904x12, 83909x12, 83912x1 |
| 8720 | MUTYH Associated Polyposis (MUTYH-2 Mutations Reflex Option to Sequence if Only 1 Mutation Found) | 83891x1, 83894x3, 83898x2, 83904x4, 83909x4, 83912x1 |
| Technique | Days |
|---|---|
| MUTYH Gene Sequence Analysis | 14-21 |
| MUTYH Associated Polyposis (MUTYH-2 Mutations Reflex Option to Sequence if Only 1 Mutation Found) | 7-21 |
1 Lipton L et al. Fam Cancer. 2006; 5(3):221-226.
2 Bisgaard ML et al. Hum Mutat. 1994; 3(2):121-125.
3 Pedace L et al. Cancer Genet Cytogenet. 2008; 182(2):130-135.
4 Gardner EJ & Richards RC. Am J Hum Genet. 1953; 5(2): 139-147.
5 Hamilton SR et al. N Engl J Med. 1995; 332(13):839-847.
6 Knudsen AL et al. Fam Cancer. 2003;2(1):43-55.
7 Fodde R et al. Nat Rev Cancer. 2001;1(1):55-67.
8 Giardiello FM et al. Gastroenterology. 2001;121(1):198-213.
9 Bunyan DJ et al. Br J Cancer. 2004; 91(6):1155-1159.
10 Sieber OM et al. Proc Nati Acad Sci USA. 2002; 99(5):2954-2958.
11 Sieber OM et al. N Engl J Med. 2003; 348:791-799.
12 Sampson JR and Jones N. Best Pract Res Clin Gastroenterol. 2009;23(2):209-18.
13 Barnetson RA et al. Clin Genet. 2007; 72:551-555.
14 Filipe B et al. Clin Genet. 2009;76: 242-255.
15 G.G.Delaini TS, G.Colucci, eds. Intestinal Polyps and Polyposis. Italy: Springer; 2009:47-57.
16 Castellsague E et al. Clin Chem. 2008; 54(7):1132-1140.