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Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome

Lorella Paparo1, Giovanni Battista Rossi2, Paolo Delrio3, Daniela Rega3, Francesca Duraturo1, Raffaella Liccardo1, Mario Debellis2, Paola Izzo1 and Marina De Rosa1*

Author Affiliations

1 Department of Molecular Medicine and Medical Biotechnology and CEINGE Biotecnologie Avanzate, University of Naples “Federico II”, Naples, Italy

2 Endoscopy Unit, Istituto Nazionale per lo studio e la cura dei tumori, “Fondazione Giovanni Pascale” IRCCS, Naples, Italy

3 Colorectal Surgical Oncology - Abdominal Oncology Department, Istituto Nazionale per lo studio e la cura dei tumori, “Fondazione Giovanni Pascale” IRCCS, Naples, Italy

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Hereditary Cancer in Clinical Practice 2013, 11:8  doi:10.1186/1897-4287-11-8

Published: 25 July 2013


Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS) and proteus syndrome are disorders known as PTEN hamartoma tumour syndrome (PHTS), that can show remarkable clinical overlap and are all caused by germline PTEN mutations.

We here present two families, one affected by CS and the other affected by BRRS, both carriers of specific pathogenetic missense mutation in exon 5 of PTEN gene, within the catalitic domain. Both PHTS families exhibited extremely variable phenotypes, showing inter- and intra- familial variability. One of the two characterised mutations, the c.320A- > T; p.107Asp- > Val, identified in the CS family, was not previously described in the literature. Furthermore, the BRRS family, carrier of the c.406 T- > C; p.136Cys- > Arg mutation, shows a substantial alteration of PTEN protein expression that well correlates with intra-familial phenotypic variability.

Finally, we describe an apparently sporadic case of an 80-year-old man, with a very low level of PTEN mRNA and protein expression, both in healthy and tumour colon mucosa, associated with a very atypical phenotype. He developed a metastatic colorectal carcinoma, macrocephaly and pheochromocytoma.

According to literature data, our observations confirm that PTEN mutations of catalytic domain can cause different syndromes. We suggest that PTEN expression could represent one of the mechanisms involved in the remarkable heterogeneity of the clinical PHTS manifestations within affected families. Furthermore, constitutive strong decrease of PTEN expression in colon normal mucosa could be associated with late onset of colorectal cancer.

PTEN hamartoma tumour syndrome (PHTS); Cowden syndrome (CS); Bannayan-riley-ruvalcaba syndrome (BRRS); Sporadic pheochromocytoma; Macrocephaly; PTEN tumour suppressor gene; Haploinsufficiency