TI: Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome.
AU: Marsh-DJ; Roth-S; Lunetta-KL; Hemminki-A; Dahia-PL; Sistonen-P; Zheng-Z; Caron-S; van-Orsouw-NJ; Bodmer-WF; Cottrell-SE; Dunlop-MG; Eccles-D; Hodgson-SV; Jarvinen-H; Kellokumpu-I; Markie-D; Neale-K; Phillips-R; Rozen-P; Syngal-S; Vijg-J; Tomlinson-IP; Aaltonen-LA; Eng-C
AD: Department of Adult Oncology and Human Cancer Genetics Unit, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
SO: Cancer-Res. 1997 Nov 15; 57(22): 5017-21
ISSN: 0008-5472
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba-Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, had previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mapping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. Lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families with JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24.
MESH: Germ-Line-Mutation; Haplotypes-; Lod-Score; Microsatellite-Repeats; Peutz-Jeghers-Syndrome-genetics
MESH: *Chromosomes,-Human,-Pair-10-genetics; *Gastrointestinal-Neoplasms-genetics; *Genes,-Suppressor,-Tumor-genetics; *Hamartoma-Syndrome,-Multiple-genetics; *Polyps-genetics
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
AN: 98037546
UD: 9802
MEDLINE EXPRESS (R) 10/97-1/98 2 of 6
TI: PTEN/MMAC1 mutations in endometrial cancers.
AU: Risinger-JI; Hayes-AK; Berchuck-A; Barrett-JC
AD: Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
SO: Cancer-Res. 1997 Nov 1; 57(21): 4736-8
ISSN: 0008-5472
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Endometrial carcinomas represent the most common gynecological cancer in the United States, yet the molecular genetic events that underlie the development of these tumors remain obscure. Chromosome 10 is implicated in the pathogenesis of endometrial carcinoma based on loss of heterozygosity (LOH), comparative genomic hybridization, and cytogenetics. Recently, a potential tumor suppressor gene, PTEN/MMAC1, with homology to dual-specificity phosphatases and to the cytoskeletal proteins tensin and auxillin was identified on chromosome 10. This gene is mutated in several types of advanced tumors that display frequent LOH on chromosome 10, most notably glioblastomas. Additionally, germ-line mutations of PTEN/MMAC1 are responsible for several familial neoplastic disorders, including Cowden disease and Bannayan-Zonana syndrome. Because this locus is included in the region of LOH in many endometrial carcinomas, we examined 70 endometrial carcinomas for alterations in PTEN/MMAC1. Somatic mutations were detected in 24 cases (34%) including 21 cases that resulted in premature truncation of the protein, 2 tumors with missense alterations in the conserved phosphatase domain, and 1 tumor with a large insertion. These data indicate that PTEN/MMAC1 is more commonly mutated than any other known gene in endometrial cancers.
MESH: Gene-Deletion; Microsatellite-Repeats-genetics
MESH: *Adenocarcinoma-genetics; *Chromosomes,-Human,-Pair-10-genetics; *Endometrial-Neoplasms-genetics; *Genes,-Suppressor,-Tumor-genetics; *Mutation-genetics
TG: Female; Human
PT: JOURNAL-ARTICLE
AN: 98014556
UD: 9801
MEDLINE EXPRESS (R) 10/97-1/98 3 of 6
TI: P-TEN, the tumor suppressor from human chromosome 10q23, is a dual-specificity phosphatase.
AU: Myers-MP; Stolarov-JP; Eng-C; Li-J; Wang-SI; Wigler-MH; Parsons-R; Tonks-NK
AD: Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
SO: Proc-Natl-Acad-Sci-U-S-A. 1997 Aug 19; 94(17): 9052-7
ISSN: 0027-8424
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Protein tyrosine phosphatases (PTPs) have long been thought to play a role in tumor suppression due to their ability to antagonize the growth promoting protein tyrosine kinases. Recently, a candidate tumor suppressor from 10q23, termed P-TEN, was isolated, and sequence homology was demonstrated with members of the PTP family, as well as the cytoskeletal protein tensin. Here we show that recombinant P-TEN dephosphorylated protein and peptide substrates phosphorylated on serine, threonine, and tyrosine residues, indicating that P-TEN is a dual-specificity phosphatase. In addition, P-TEN exhibited a high degree of substrate specificity, showing selectivity for extremely acidic substrates in vitro. Furthermore, we demonstrate that mutations in P-TEN, identified from primary tumors, tumor cells lines, and a patient with Bannayan-Zonana syndrome, resulted in the ablation of phosphatase activity, demonstrating that enzymatic activity of P-TEN is necessary for its ability to function as a tumor suppressor.
MESH: Amino-Acid-Sequence; Enzyme-Activation; Molecular-Sequence-Data; Mutation-; Phosphoprotein-Phosphatase-metabolism; Phosphorylation-; Protein-Tyrosine-Phosphatase-metabolism; Substrate-Specificity
MESH: *Chromosomes,-Human,-Pair-10; *Genes,-Suppressor,-Tumor; *Phosphoprotein-Phosphatase-genetics; *Protein-Tyrosine-Phosphatase-genetics
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA53840CANCI; GM55989GMNIGMS; 5T32CA0931118CANCI
RN: EC 3.1.3.-; EC 3.1.3.16; EC 3.1.3.48
NM: P-TEN-phosphatase; Phosphoprotein-Phosphatase; Protein-Tyrosine-Phosphatase
AN: 97404346
UD: 9711
MEDLINE EXPRESS (R) 10/97-1/98 4 of 6
TI: [Neurocutaneous syndromes with vascular alterations]
TO: Sindromes neurocutaneos con afectacion vascular.
AU: de-Felipe-I; Quintanilla-E
AD: Departamento de Dermatologia, Clinica Universitaria de Navarra, Pamplona, Espana.
SO: Rev-Neurol. 1997 Sep; 25 Suppl 3: S250-8
ISSN: 0210-0010
PY: 1997
LA: SPANISH; NON-ENGLISH
CP: SPAIN
AB: There are several syndromes in which neurological and cutaneous alterations of vascular origin, among other symptoms, occur. The key point of this fact is that these cutaneous signs permit early diagnosis, thus helping in further recognition of more complex syndromes and preventing unnecessary, harmful and costly diagnostic procedures or having to wait until the appearance of neurological signs. Therefore, these diseases should be classified attending to the most notorious vascular lesions they show, though they may show other less frequent cutaneous vascular lesions. In this way, these syndromes can be classified as associated with nevus flammeus (Sturge-Weber, Shapiro-Shulman, Bonnet-Dechaume-Blanc, Cobb, Klippel-Trenaunay, Fegeler, Robert), cavernous hemangiomas (Maffucci, blue-rubber-bleb-nevus, Proteus, Bannayan-Zonana, Riley-Smith, familial cavernous angiomatosis, POEMS syndrome), capillary hemangiomas (Rubinstein-Tayabi, Coffin-Siris, PHACE syndrome), telangiectasia (congenital telangiectatic cutis marmorata, Rendu-Osler-Weber, ataxia telangiectasia, Cockayne, De Sanctis-Cacchione), livedo reticularis (Sneddon, Divry-van-Bogaert), angioqueratoma (Fabry disease, Fucosidosis) and hemangioblastoma (Von Hippel-Lindau). Though we have tried that these vascular lesions should be named as angiomas if they are malformations and hemangiomas if they are benign neoplasias, they are called following morphological aspects rather than other criteria, due to their unknown origin.
MESH: Brain-Neoplasms-complications; English-Abstract; Facial-Neoplasms-complications; Hemangioma-complications; Skin-Diseases,-Vascular-complications; Syndrome-
MESH: *Skin-Diseases,-Vascular-diagnosis
TG: Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
AN: 97383900
UD: 9710
MEDLINE EXPRESS (R) 10/97-1/98 5 of 6
TI: Germline mutations in PTEN are present in Bannayan-Zonana syndrome [letter]
AU: Marsh-DJ; Dahia-PL; Zheng-Z; Liaw-D; Parsons-R; Gorlin-RJ; Eng-C
SO: Nat-Genet. 1997 Aug; 16(4): 333-4
ISSN: 1061-4036
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
MESH: Base-Sequence; DNA-; Genes,-Suppressor,-Tumor; Hamartoma-Syndrome,-Multiple-enzymology; Molecular-Sequence-Data
MESH: *Chromosomes,-Human,-Pair-10; *Germ-Line-Mutation; *Hamartoma-Syndrome,-Multiple-genetics; *Phosphoprotein-Phosphatase-genetics
TG: Animal; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: LETTER
CN: 1P30AG1331401AGNIA
RN: EC 3.1.3.16; 9007-49-2
NM: Phosphoprotein-Phosphatase; DNA
AN: 97385233
UD: 9710
SI: GENBANK/U92436; GENBANK/U93051; GENBANK/U92437; GENBANK/U92435
MEDLINE EXPRESS (R) 1992-1996 6 of 6
TI: Clinicopathologic findings in the Bannayan-Riley-Ruvalcaba syndrome.
AU: Fargnoli-MC; Orlow-SJ; Semel-Concepcion-J; Bolognia-JL
AD: Department of Dermatology, Yale University School of Medicine, New Haven, Conn, USA.
SO: Arch-Dermatol. 1996 Oct; 132(10): 1214-8
ISSN: 0003-987X
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases.
MESH: Abnormalities,-Multiple-genetics; Adolescence-; Adult-; Bone-and-Bones-abnormalities; Head-abnormalities; Mental-Retardation-genetics; Skin-pathology; Skin-Diseases-genetics; Skin-Diseases-pathology; Syndrome-
MESH: *Abnormalities,-Multiple; *Mental-Retardation; *Skin-Diseases
TG: Case-Report; Female; Human; Male
PT: JOURNAL-ARTICLE
AN: 97012217
UD: 9701
SB: AIM