Myriad Adds 6 Genes to the myRisk Hereditary Cancer Panel

Myriad Genetic Laboratories, Inc. is excited to announce the addition of six new genes to the Myriad myRisk Hereditary Cancer Panel. Beginning February 20, 2019, the analysis of AXIN2, MSH3[1], RPS20, GALNT12, NTHL1, and RNF43 will be added to the myRisk panel. The myRisk panel test will include sequencing and large rearrangement analysis of the six genes in order to accommodate new information that may impact patient care.

AXIN2

Studies have shown mutations in AXIN2 to be associated with an elevated risk of colorectal cancer which is significantly higher than the general population[2]. Oligodontia (missing teeth) has also been identified as a feature among patients who carry a mutation. NCCN guidelines recommend that patients who carry a mutation in AXIN2 begin colonoscopies between 25 and 30 years of age.

MSH3

Studies have shown that biallelic mutations of the MSH3 gene are associated with an elevated risk of polyposis and colorectal cancer[3]. Other features may include duodenal polyps, astrocytoma, thyroid adenoma, and uterine leiomyoma, but further studies are needed to confirm this. NCCN guidelines recommend that patients who carry biallelic mutations in MSH3 begin colonoscopies between 25 and 30 years of age and colorectal surgical evaluation based on cancer diagnosis or polyp number and size. Monoallelic mutations in MSH3 are not currently believed to be associated with an increased risk and do not have supported changes to treatment or management.

NTHL1

Studies have shown biallelic mutations in NTHL1 are associated with an elevated risk of attenuated adenomatous polyposis and colorectal cancer[4].  There have been suggestions of other cancers, but further studies are needed to confirm this. NCCN guidelines recommend that patients who carry a mutation in NTHL1 begin colonoscopies between 25 and 30 years of age and colorectal surgical evaluation based on cancer diagnosis or polyp number and size. Similar to MSH3, monoallelic mutations in NTHL1 are not currently associated with increased risk and do not have supported changes to treatment or management.

RNF43

Mutations in the RNF43 gene are associated with an elevated risk of Serrated Polyposis Syndrome (SPS), a colorectal cancer syndrome characterized by sessile serrated polyps in the colon and/or rectum[5] and colorectal cancer.  NCCN guidelines recommend that patients who carry a mutation in RNF43 and meet the WHO’s criteria for Serrated Polyposis Syndrome start colonoscopies at a younger age[6]. These criteria are:

  1. At least five serrated polyps proximal to the sigmoid colon, two of which are greater than 10 mm in diameter
  2. Any number of serrated polyps occurring proximal to the sigmoid colon in an individual who has a first-degree relative with serrated polyposis
  3. More than 20 serrated polyps of any size distributed throughout the colon

GALNT12

Studies have shown mutations in the GALNT12 gene are associated with an elevated risk of colorectal cancer[7] and have been associated with an increased risk of attenuated polyposis[8]. Currently there are no medical management guidelines for colorectal cancer risk in mutation carriers; however, the possibility of an increased risk for colorectal cancer may warrant consideration of individualized screening and/or risk reduction strategies such as the modification of standard population screening by starting screening at younger ages and/or performing screenings at greater frequency.

RPS20

According to clinical studies, mutations in RPS20 are associated with an elevated risk of colorectal cancer[9]. There are currently no guidelines for the medical management of individuals with mutations in RPS20. Since information about the cancer risks associated with RPS20 mutations is relatively new – with uncertainty about the best ways to reduce these risks – it may be appropriate to interpret these results in consultation with cancer genetics professionals who have expertise in this emerging area of knowledge.

[1] Analysis of the six genes will include full sequencing and large rearrangement. Part of MSH3 exon 1 with a repetitive region will be omitted from analysis

[2] Mutations in AXIN2 Cause Familial Tooth Agenesis and Predispose to Colorectal Cancer
Lammi et al.2004 Am J Hum Genet

[3] Exome Sequencing Identifies Biallelic MSH3 Germline Mutations as a Recessive Subtype of Colorectal Adenomatous Polyposis
Adam et al.2016 Am J Hum Genet

[4] A germline homozygous mutation in the BER gene NTHL1 causes adenomatous polyposis and colorectal Cancer
Weren et al., 2015 Nature Genetics

[5] RNF43 Germline and Somatic Mutation in Serrated Neoplasia Pathway and its Associated with BRAF Mutation
Yan et al. 2016 Gut

[6] Serrated polyposis syndrome: molecular, pathological and clinical aspects 

Guarinos, Carla et al. 2012 World Journal of Gastroenterology

[7] Inherited Deleterious Variants in GALNT12 are Associated with CRC Susceptibility
Clarke et al. 2012 HuMu

[8]Role of GALNT12 in the genetic predisposition to attenuated adenomatous polyposis syndrome

Lorca et al. 2017 PLoS one

[9] Germline Mutation of RPS20, Encoding a Ribosomal Protein, Causes Predisposition to Hereditary Nonpolyposis Colorectal Carcinoma Without DNA Mismatch Repair Deficiency
Taina et al. 2014 Gastroenterology

 

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