PMID- 10400993
OWN - NLM
STAT- MEDLINE
DCOM- 19990914
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 8
DP  - 1999 Aug
TI  - PTEN mutation spectrum and genotype-phenotype correlations in
      Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome.
PG  - 1461-72
AB  - Germline mutations in the tumour suppressor gene PTEN have been implicated in two
      hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and 
      Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual
      specificity phosphatase, a substrate of which is phosphatidylinositol
      3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. 
      CS is characterized by multiple hamartomas and an increased risk of benign and
      malignant disease of the breast, thyroid and central nervous system, whilst the
      presence of cancer has not been formally documented in BRR. The partial clinical 
      overlap in these two syndromes is exemplified by the hallmark features of BRR:
      macrocephaly and multiple lipomas, the latter of which occur in a minority of
      individuals with CS. Additional features observed in BRR, which may also occur in
      a minority of CS patients, include Hashimoto's thyroiditis, vascular
      malformations and mental retardation. Pigmented macules of the glans penis,
      delayed motor development and neonatal or infant onset are noted only in BRR. In 
      this study, constitutive DNA samples from 43 BRR individuals comprising 16
      sporadic and 27 familial cases, 11 of which were families with both CS and BRR,
      were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR
      cases. 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). Additionally, the presence of
      lipomas was correlated with the presence of PTEN mutation in BRR patients ( P =
      0.028). In contrast to a prior report, no significant difference in mutation
      status was found in familial versus sporadic cases of BRR ( P = 0.113).
      Comparisons between BRR and a previously studied group of 37 CS families
      suggested an increased likelihood of identifying a germline PTEN mutation in
      families with either CS alone or both CS and BRR when compared with BRR alone ( P
      = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation
      positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS
      and BRR may be different presentations of a single syndrome and, hence, both
      should receive equal attention with respect to cancer surveillance.
FAU - Marsh, D J
AU  - Marsh DJ
AD  - Clinical Cancer Genetics and Human Cancer Genetics Programs, Ohio State
      University Comprehensive Cancer Center, 690C Medical Research Facility, 420 West 
      12th Avenue, Columbus, OH 43210, USA.
FAU - Kum, J B
AU  - Kum JB
FAU - Lunetta, K L
AU  - Lunetta KL
FAU - Bennett, M J
AU  - Bennett MJ
FAU - Gorlin, R J
AU  - Gorlin RJ
FAU - Ahmed, S F
AU  - Ahmed SF
FAU - Bodurtha, J
AU  - Bodurtha J
FAU - Crowe, C
AU  - Crowe C
FAU - Curtis, M A
AU  - Curtis MA
FAU - Dasouki, M
AU  - Dasouki M
FAU - Dunn, T
AU  - Dunn T
FAU - Feit, H
AU  - Feit H
FAU - Geraghty, M T
AU  - Geraghty MT
FAU - Graham, J M Jr
AU  - Graham JM Jr
FAU - Hodgson, S V
AU  - Hodgson SV
FAU - Hunter, A
AU  - Hunter A
FAU - Korf, B R
AU  - Korf BR
FAU - Manchester, D
AU  - Manchester D
FAU - Miesfeldt, S
AU  - Miesfeldt S
FAU - Murday, V A
AU  - Murday VA
FAU - Nathanson, K L
AU  - Nathanson KL
FAU - Parisi, M
AU  - Parisi M
FAU - Pober, B
AU  - Pober B
FAU - Romano, C
AU  - Romano C
FAU - Eng, C
AU  - Eng C
AU  - et al.
LA  - eng
GR  - P30 CA16058/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Genetic Markers)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Abnormalities, Multiple/*genetics/pathology
MH  - Cells, Cultured
MH  - Chromosome Deletion
MH  - Chromosome Mapping
MH  - Chromosomes, Human, Pair 10/genetics
MH  - Cohort Studies
MH  - Craniofacial Abnormalities/genetics
MH  - Family Health
MH  - Female
MH  - Genetic Carrier Screening
MH  - Genetic Markers
MH  - Genotype
MH  - Germ-Line Mutation
MH  - Hamartoma Syndrome, Multiple/*genetics/pathology
MH  - Heterozygote
MH  - Humans
MH  - Intellectual Disability/genetics
MH  - Male
MH  - Mutation
MH  - PTEN Phosphohydrolase
MH  - Pedigree
MH  - Phenotype
MH  - Phosphoric Monoester Hydrolases/*genetics
MH  - Syndrome
MH  - *Tumor Suppressor Proteins
EDAT- 1999/07/13 10:00
MHDA- 2001/03/28 10:01
CRDT- 1999/07/13 10:00
PHST- 1999/07/13 10:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1999/07/13 10:00 [entrez]
AID - ddc155 [pii]
AID - 10.1093/hmg/8.8.1461 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Aug;8(8):1461-72. doi: 10.1093/hmg/8.8.1461.