Sorted By Test Name - Mayo Medical Laboratories

KRAS
89378
reliable for detection of carriers of Krabbe disease. Molecular genetic testing (this test) is the
recommended test for individuals with a family history of Krabbe disease in which the mutations in the
family are known. The recommended molecular test if mutations in the family are not known is
GALCS/60696 Krabbe Disease, Full Gene Analysis and Large (30 kb) Deletion, PCR. This assay tests for
specific mutations previously identified in a family member and, therefore, may also be used for
diagnosing individuals with a suspected diagnosis of Krabbe disease when mutations in the family are
known. While enzyme activity is not predictive of age of onset, there are known genotype-phenotype
correlations. The common 30-kb deletion spanning intron 10 through the end of the gene accounts for a
significant proportion of disease alleles that contribute to infantile Krabbe disease. Individuals who are
homozygous for the deletion, or compound heterozygous for the deletion and a second GALC mutation
(with the exception of late-onset mutations), are predicted to have infantile Krabbe disease. The
c.857G->A (p.Gly286Asp) mutation, on the other hand, is only associated with a late-onset phenotype.
Useful For: Carrier testing of individuals with a family history of Krabbe disease when a mutation(s)
has been identified in an affected family member Diagnostic confirmation of Krabbe disease when
familial mutations have been previously identified
Interpretation: An interpretive report will be provided.
Reference Values:
An interpretive report will be provided.
Clinical References: 1. Wenger DA: Krabbe Disease (Most recent review March 2011). Available at
http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=krabbe 2. Luzi P, Rafi MA, Wenger
DA: Structure and organization of the human galactocerebrosidase (GALC) gene. Genomics
1995;26:407-409 3. Luzi P, Rafi MA, Wenger DA: Characterization of the large deletion in the GALC
gene found in patients with Krabbe disease. Hum Mol Genet 1995;4(12):2335-2338 4. Spiegel R, Bach G,
Sury V, et al: A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as
Krabbe disease: report of saposin A deficiency in humans. Molec Genet Metab 2005,84:160-166
KRAS Gene, 7 Mutation Panel, Tumor
Clinical Information: Colorectal cancer is currently 1 of the most common malignancies diagnosed
each year. Strategies that focus on early detection and prevention effectively decrease the risk of mortality
associated with the disease. In addition, an increase in survival rate for individuals with stage II and III
colorectal cancer has been observed as a result of advancements in standard chemotherapeutic agents and
the development of specialized targeted therapies. Monoclonal antibodies against epidermal growth factor
receptor (EGFR), such as cetuximab and panitumumab, represent a new area of targeted therapy for such
patients. However, studies have shown that not all individuals with colorectal cancer respond to these
EGFR-targeted molecules. Because the combination of targeted therapy and standard chemotherapy leads
to an increase in toxicity and cost, strategies that help to identify the individuals most likely to benefit
from such targeted therapies are desirable. EGFR is a growth factor receptor that is activated by the
binding of specific ligands (epiregulin and amphiregulin), resulting in activation of the RAS/MAPK
pathway. Activation of this pathway induces a signaling cascade ultimately leading to cell proliferation.
Dysregulation of the RAS/MAPK pathway is a key factor in tumor progression. Targeted therapies
directed to EGFR, which inhibit activation of the RAS/MAPK pathway, have demonstrated some success
(increased progression-free and overall survival) in treating patients with colorectal cancer. One of the
most common somatic alterations in colon cancer is the presence of activating mutations in the
proto-oncogene KRAS. KRAS is recruited by ligand-bound (active) EGFR to initiate the signaling
cascade induced by the RAS/MAPK pathway. Because mutant KRAS constitutively activates the
RAS/MAPK pathway downstream of EGFR, agents such as cetuximab and panitumumab which prevent
ligand-binding to EGFR, do not appear to have any meaningful inhibitor activity on cell proliferation in
the presence of mutant KRAS. Current data suggest that the efficacy of EGFR-targeted therapies in colon
cancer is confined to patients with tumors lacking KRAS mutations. As a result, the mutation status of
KRAS can be a useful marker by which patients are selected for EGFR-targeted therapy in combination
with standard chemotherapy.
Useful For: Prognostic markers for cancer patients treated with epidermal growth factor
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