Furthermore, we review the PTEN mutation positive BRRS cases, to further delineate the phenotype and to compare the cases with a genomic deletion with the cases with a point mutation.
PTEN, encoding a dual phosphatase tumor suppressor, is mutated in 85 and 65% of individuals with Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS), respectively.
Germline PTEN mutations cause Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR), two hamartoma-tumour syndromes, and somatic PTEN alterations have been shown to participate, to a greater or lesser extent, in a wide variety of sporadic neoplasia.
We have shown that germline mutations of PTEN are present in individuals with two hamartoma syndromes: Cowden Syndrome, associated with a predisposition to breast and thyroid cancers, and Bannayan-Zonana syndrome.
This case highlights the importance of early screening for PTEN mutations in cases of hemimegalencephaly not otherwise explained by another disorder, even in the absence of signs of Proteus syndrome or the full manifestations of Bannayan-Riley Ruvalcaba syndrome.
Genital lentigines in a 6-year-old boy with a family history of Cowden's disease: clinical and genetic evidence of the linkage between Bannayan-Riley-Ruvacalba syndrome and Cowden's disease.
Molecular testing of the PTEN gene (phosphatase and tensin homolog protein) revealed a R355X mutation, consistent with the diagnosis of Bannayan-Riley-Ruvalcaba Syndrome (BRRS).
Moreover, germline mutation of PTEN leads to the development of the related hereditary cancer predisposition syndromes, Cowden disease, and Bannayan-Zonana syndrome, wherein breast and thyroid cancer incidence is elevated.
Germline mutations in the PTEN gene have recently been identified in some individuals with Cowden disease (CD), Lhermitte-Duclos disease (LDD), and Bannayan-Zonana syndrome.
Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024).
These data suggest that the previously reported case of LCHAD and BRRS either represents the coincidental concurrence of two rare genetic events or that a gene other than PTEN is related to LCHAD and BRRS.
We show that cell lines from Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients with germ line PTEN promoter mutations in the vicinity of the p53-binding motifs have altered p53 regulation.
Germline mutations in PTEN, that encodes a dual-specificity phosphatase, have been implicated in two hamartoma-tumor syndromes that exhibit some clinical overlap, Cowden syndrome and Bannayan-Zonana syndrome.
We therefore sought to characterize the relative expression of 5', middle, and 3' full-length PTEN mRNA (FL-PTEN) and also of these eight PTEN SVs in 85 (65 female and 20 male) patients with CS/BRRS (with or without PTEN mutations) compared with 27 controls, using a SYBR green quantitative polymerase chain reaction method.
PTEN is a tumor suppressor gene mutated in many human sporadic cancers and in hereditary cancer syndromes such as Cowden disease, Bannayan-Zonana syndrome and Lhermitte-Duclos disease.
Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers.