Germline PTEN mutation Cowden syndrome: An under-appreciated form of hereditary kidney cancer - Abstract

INTRODUCTION: Cowden syndrome (CS) is a hereditary cancer syndrome associated with a germline mutation in PTEN.

Patients are predisposed to multiple malignancies including renal cell carcinoma (RCC).

METHODS: Patients with CS were evaluated as part of a clinical protocol. Those with a history of RCC underwent review of clinical features, tumor characteristics, and family history. Renal tumors were evaluated for loss of heterozygosity (LOH).

RESULTS: Among 24 CS patients, 4 were identified with RCC (16.7%). Three patients had solitary tumors, two with papillary type I histology and one with clear cell histology. The fourth patient had bilateral, synchronous chromophobe tumors. No patients had a prior family history of RCC. All RCC patients had dermatologic manifestations of CS and had macrocephaly. LOH at the PTEN mutation was identified in 4 tumors (80%). No genotype-phenotype association was found, as the same mutation was identified in different RCC histologies.

CONCLUSION: RCC is an underappreciated feature of CS. As most patients lack a prior family history or a distinctive RCC histology, recognition of the associated non-renal features should target referral for genetic counseling. PTEN LOH is common in CS renal tumors. Because loss of PTEN can activate mTOR and mTOR inhibitors are FDA-approved to treat RCC, these agents have clinical potential in RCC associated with CS.

Written by:
Shuch B, Ricketts CJ, Vocke CD, Komiya T, Middelton LA, Kauffman EC, Merino MJ, Metwalli AR, Dennis P, Linehan WM.   Are you the author?
Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Reference: J Urol. 2013 Jun 10. pii: S0022-5347(13)04582-5.
doi: 10.1016/j.juro.2013.06.012


PubMed Abstract
PMID: 23764071

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