RGD Reference Report - Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer. - Rat Genome Database

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Silencing of the PTEN tumor-suppressor gene in anaplastic thyroid cancer.

Authors: Frisk, Tony  Foukakis, Theodoris  Dwight, Trisha  Lundberg, Jonas  Höög, Anders  Wallin, Göran  Eng, Charis  Zedenius, Jan  Larsson, Catharina 
Citation: Frisk T, etal., Genes Chromosomes Cancer. 2002 Sep;35(1):74-80.
RGD ID: 12832749
Pubmed: PMID:12203792   (View Abstract at PubMed)
DOI: DOI:10.1002/gcc.10098   (Journal Full-text)

Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, and thyroid tumors of follicular epithelium. PTEN has also been found to be somatically deleted, mutated, and/or silenced in various sporadically occurring cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma, and endometrial cancer. Loss or reduction of PTEN protein expression as well as inappropriate subcellular compartmentalization is seen in non-medullary thyroid cancers. However, although allelic loss of the PTEN locus in 10q23.3 is frequently seen, this is not coupled with mutations in the PTEN gene. To approach further the frequency and mechanism behind PTEN silencing, we screened a panel of 87 sporadic thyroid tumors for PTEN mRNA expression, including 14 anaplastic carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 ordinary adenomas. Complete loss of PTEN mRNA expression was evident in six of the tumors, including four anaplastic carcinomas, one widely invasive carcinoma, and one ordinary adenoma. The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors. No association was observed between the expression, loss of heterozygosity, and mutation status in the 33 cases in which these parameters were compared. This indicates that PTEN silencing is a result of a wide variety of epigenetic and/or structural silencing mechanisms rather than a consequence of structural biallelic inactivation of the classical type. Furthermore, the high rate of alterations in the 10q23 region might indicate the presence of an as-yet unknown tumor-suppressor gene with an important role in the development of thyroid tumors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Thyroid Neoplasms severityIEP 12832749mRNA:decreased expression:thyroid gland (human)RGD 
Thyroid Neoplasms severityISOPTEN (Homo sapiens)12832749; 12832749mRNA:decreased expression:thyroid gland (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
PTEN  (phosphatase and tensin homolog)


Additional Information