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ARLTS1 Trp149Stop Mutation and the Risk of Ovarian Cancer

Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio

In Response:

We completely agree with Masojc et al. that "Trp149Stop is a mutation" yielding a dysfunctional product with a role in tumorigenesis. Moreover, their data reporting comparable frequency of ARLTS1 Trp149Stop variant in unselected ovarian cancers and controls agrees with our initial observations that the frequency of this variant is similar in patients with sporadic cancer and control cases (1).

We also proposed that down-regulation of ARLTS1 by deletion and/or hypermethylation is a frequent event in sporadic cancers, including ovarian cancers, and that this mechanism may represent the counterpart of ARLTS1 mutations observed with increased frequency in familial cancers (1, 2). In support of ARLTS1 involvement in familial cancer predisposition, a second variant (Cys¹⁴⁸Arg) has been shown to confer increased risk for familial breast cancer (3).

In the light of two studies by Frank et al. linking Trp149Stop variant to increased risk of familial breast cancer in BRCA1-negative and BRCA2-negative families (4) and bilateral breast cancer (3), it would be interesting to determine the difference in Trp149Stop frequency between sporadic and familial ovarian tumors in various human populations.

References

1. Calin GA, Trapasso F, Masayoshi S, et al. Familial cancer associated with a polymorphism in ARLTS1. N Engl J Med 2005;352:1667–76.[Abstract/Free Full Text]
2. Petrocca F, Iliopoulos D, Qin HR, et al. Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer. Cancer Res 2006;66:10287–91.[Abstract/Free Full Text]
3. Frank B, Hemminki K, Meindl A, et al. Association of the ARLTS1 Cys¹⁴⁸Arg variant with familial breast cancer risk. Int J Cancer 2005;118:2505–8.[CrossRef]
4. Frank B, Klaes R, Burwinkel B. Familial cancer and ARLTS1. N Engl J Med 2005;353:313–4.[Free Full Text]

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