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

Lorella Paparo, Giovanni Battista Rossi, Paolo Delrio, Daniela Rega, Francesca Duraturo, Raffaella Liccardo, Mario Debellis, Paola Izzo, Marina De Rosa

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15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number8
JournalHereditary Cancer in Clinical Practice
Volume11
Issue number1
DOIs
Publication statusPublished - Jul 25 2013

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Multiple Hamartoma Syndrome
Gene Expression
PTEN Phosphohydrolase
Mutation
Colorectal Neoplasms
Colon
Mucous Membrane
Proteus Syndrome
Megalencephaly
Phenotype
Germ-Line Mutation
Pheochromocytoma
Missense Mutation
Exons
Catalytic Domain

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Genetics(clinical)

Cite this

@article{b22ba9fe0a1945f2bafc027c2aa0cc71,
title = "Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome",
abstract = "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.",
keywords = "Bannayan-riley-ruvalcaba syndrome (BRRS), Cowden syndrome (CS), Haploinsufficiency, Macrocephaly, PTEN hamartoma tumour syndrome (PHTS), PTEN tumour suppressor gene, Sporadic pheochromocytoma",
author = "Lorella Paparo and Rossi, {Giovanni Battista} and Paolo Delrio and Daniela Rega and Francesca Duraturo and Raffaella Liccardo and Mario Debellis and Paola Izzo and {De Rosa}, Marina",
year = "2013",
month = "7",
day = "25",
doi = "10.1186/1897-4287-11-8",
language = "English",
volume = "11",
journal = "Hereditary Cancer in Clinical Practice",
issn = "1731-2302",
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T1 - Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome

AU - Paparo, Lorella

AU - Rossi, Giovanni Battista

AU - Delrio, Paolo

AU - Rega, Daniela

AU - Duraturo, Francesca

AU - Liccardo, Raffaella

AU - Debellis, Mario

AU - Izzo, Paola

AU - De Rosa, Marina

PY - 2013/7/25

Y1 - 2013/7/25

N2 - 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.

AB - 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.

KW - Bannayan-riley-ruvalcaba syndrome (BRRS)

KW - Cowden syndrome (CS)

KW - Haploinsufficiency

KW - Macrocephaly

KW - PTEN hamartoma tumour syndrome (PHTS)

KW - PTEN tumour suppressor gene

KW - Sporadic pheochromocytoma

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U2 - 10.1186/1897-4287-11-8

DO - 10.1186/1897-4287-11-8

M3 - Article

VL - 11

JO - Hereditary Cancer in Clinical Practice

JF - Hereditary Cancer in Clinical Practice

SN - 1731-2302

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M1 - 8

ER -