Table of Contents
1
UI - 11753655
AU - Ling G; Ahmadian A; Persson A; Unden AB; Afink G; Williams C; Uhlen M;
TI -
Toftgard R; Lundeberg J; Ponten F
PATCHED and p53 gene alterations in sporadic and hereditary basal cell
cancer.
SO - Oncogene 2001 Nov 22;20(53):7770-8
AD - Department of Genetics and Pathology, Rudbeck Laboratory, University
Hospital, Uppsala University, S-751 85 Uppsala, Sweden.
It is widely accepted that disruption of the hedgehog-patched pathway is
a key event in development of basal cell cancer. In addition to patched
gene alterations, p53 gene mutations are also frequent in basal cell
cancer. We determined loss of heterozygosity in the patched and p53 loci
as well as sequencing the p53 gene in tumors both from sporadic and
hereditary cases. A total of 70 microdissected samples from tumor and
adjacent skin were subjected to PCR followed by fragment analysis and
DNA sequencing. We found allelic loss in the patched locus in 6/8
sporadic basal cell cancer and 17/19 hereditary tumors. All sporadic and
7/20 hereditary tumors showed p53 gene mutations. Loss of heterozygosity
in the p53 locus was rare in both groups. The p53 mutations detected in
hereditary tumors included rare single nucleotide deletions and unusual
double-base substitutions compared to the typical ultraviolet light
induced missense mutations found in sporadic tumors. Careful
microdissection of individual tumors revealed genetically linked
subclones with different p53 and/or patched genotype providing an
insight on time sequence of genetic events. The high frequency and
co-existence of genetic alterations in the patched and p53 genes suggest
that both these genes are important in the development of basal cell
cancer.
2
UI - 11765170
AU - Tumer C; Er N; Balci S; Atac A
TI -
Two male patients with nevoid basal cell carcinoma syndrome from Turkey.
SO - Turk J Pediatr 2001 Oct-Dec;43(4):351-5
AD - Department of Oral Surgery, Faculty of Dentistry, Hacettepe University,
Ankara, Turkey.
Nevoid basal cell carcinoma syndrome, also known as Gorlin's syndrome,
is a familial autosomal dominant syndrome characterized by multiple
basal cell carcinomas, multiple odontogenic keratocysts of the jaws, and
skeletal anomalies. Both tumors and malformations of the central nervous
system occur with nevoid basal cell carcinoma. Medulloblastoma is the
primary brain tumor most frequently associated with this syndrome. The
authors report in this article two male patients with nevoid basal cell
carcinoma syndrome: a 22-year-old male patient with multiple odontogenic
keratocysts, who had medulloblastoma at two years and multiple basal
cell carcinoma at 10 years of age, and a 15-year-old male patient with
skeletal abnormalities and multiple odontogenic keratocysts in the jaws.
3
UI - 1741977
AU - Grubben C; Fryns JP; Smeets E; Van den Berghe H
TI -
Noonan phenotype in the basal cell nevus syndrome.
SO - Genet Couns 1991;2(1):47-54
AD - Center for Human Genetics, University of Leuven, Belgium.
In this report we present a three-generation family in which five
members present the basal cell nevus syndrome. In three of them a Noonan
phenotype was present. The basal cell nervus syndrome is another example
of a neural crest dysplasia associated with a Noonan-like phenotype.
This observation supports the theory that the autosomal dominant
mutation causing the neural crest dysplasia may lead to a Noonan-like
phenotype.
4
UI - 3719181
AU - Goffin M; Leys A; Vanuytrecht-Henderickx D; Degreef H; Missotten L
TI -
Eye defects with the basal cell nevus syndrome.
SO - Bull Soc Belge Ophtalmol 1986;213():87-92
5
UI - 3755786
AU - Knobber D; Enderer K; Kloppenburg W; Bertram G; Rose KG
TI -
[Stapes anomaly, Gorlin-Goltz and hand-foot-uterus syndrome as partial
aspects of a generalized ectodermal-mesodermal abnormality syndrome with
variable expression]
SO - Laryngol Rhinol Otol (Stuttg) 1986 Jun;65(6):305-8
A case of a Gorlin-Goltz-syndrome with anomalies of the stapes and incus
of one ear is described for the first time. In the reported case, the
hand-foot-uterus-syndrome could be recognised simultaneously. In the
literature, about 250 cases of the syndrome are known, first published
by Gorlin and Goltz in 1960. Malformations of the middle ear, however,
have not yet been described in the Gorlin-Goltz-syndrome. As in the
reported case both of the syndromes, the Gorlin-Goltz-syndrome and the
hand-foot-uterus-syndrome, could be diagnosed, it must be discussed
whether there are two independent syndromes or only one syndrome of
polyvalent malformations characterised by variable expressivity.
6
UI - 7856756
AU - Schofield D; West DC; Anthony DC; Marshal R; Sklar J
TI -
Correlation of loss of heterozygosity at chromosome 9q with histological
subtype in medulloblastomas.
SO - Am J Pathol 1995 Feb;146(2):472-80
AD - Department of Pathology, Brigham and Women's Hospital, Boston,
Massachusetts.
Patients with the nevoid basal cell carcinoma syndrome (NBCCS) are at
increased risk for medulloblastomas as well as for basal cell
carcinomas. The gene for NBCCS has been mapped to chromosome 9q22.3-q31
by linkage analysis, and loss of heterozygosity (LOH) in this region has
been demonstrated in approximately one-half of sporadic basal cell
carcinomas. In the present study, LOH for chromosome 9q22.3-q31
microsatellite markers was investigated in medulloblastomas occurring
among children with NBCCS and in sporadic medulloblastomas.
Histologically, all 3 NBCCS medulloblastomas were noted to have a
desmoplastic phenotype, and LOH was detected in both of the 2 cases for
which microsatellite markers were heterozygous in normal tissues. LOH
was also detected in a subset of sporadic medulloblastomas, each of
which were found to display the desmoplastic phenotype. In all, 3 of the
6 sporadic desmoplastic tumors showed LOH, whereas LOH was not seen in
any of the 11 sporadic, non-desmoplastic medulloblastomas studied.
Additionally, desmoplastic tumors lacking detectable LOH each showed
histological features of so-called cerebellar neuroblastoma, a subgroup
of desmoplastic medulloblastoma with extensive neuroblastomatous
differentiation. The data are consistent with a role for inactivation of
a tumor suppressor gene at chromosome 9q in the development of
medulloblastomas in patients with NBCCS and of sporadic medulloblastomas
characterized by a desmoplastic phenotype similar to that found in
patients with NBCCS. Restriction of chromosome 9q loss to
non-neuroblastomatous desmoplastic tumors suggests that this variant of
medulloblastoma maybe pathogenetically distinct from tumors having other
histological phenotypes.
7
UI - 8713665
AU - Kovacs A; Czeizel E
TI -
[Six cases of basal cell nevus carcinoma in three families]
SO - Orv Hetil 1996 Mar 10;137(10):513-22
AD - Komarom-Esztergom Megyei Onkormanyzat Korhaza es Rendelointezete,
Tatabanya, Szent Borbala Korhaz, Borgyogyaszati Osztaly es Bor es
Nemibeteggondozo Intezet.
Six cases of three families had basal cell nevus cacinoma syndrome of
autosomal dominant inheritance. Five characteristics of this genetic
disease are stressed: (1) 40% of cases had sporadic occurrence due to de
novo mutations; (2) there are three phases in the manifestation of the
disease: congenital abnormalities diagnosed after birth; nevoid phase
during childhood with increase at adolescence; oncogen phase after the
second decade; (3) symptoms have a variability and age-dependency, (4)
this mutant gene can cause both congenital abnormalities and tumours;
(5) these patients are very sensitive for environmental mutagens thus it
is necessary to limit or to exclude UV and X-rays, cytostatic and
immunosuppressive drug treatments.
8
UI - 8755929
AU - Shimkets R; Gailani MR; Siu VM; Yang-Feng T; Pressman CL; Levanat S;
TI -
Goldstein A; Dean M; Bale AE
Molecular analysis of chromosome 9q deletions in two Gorlin syndrome
patients.
SO - Am J Hum Genet 1996 Aug;59(2):417-22
AD - Department of Genetics, Yale University School of Medicine, New Haven,
CT 06520-8005, USA.
Gorlin syndrome is an autosomal dominant disorder characterized by
multiple basal cell carcinomas, medulloblastomas, ovarian fibromas, and
a variety of developmental defects. All affected individuals share
certain key features, but there is significant phenotypic variability
within and among kindreds with respect to malformations. The gene
(NBCCS) maps to chromosome 9q22, and allelic loss at this location is
common in tumors from Gorlin syndrome patients. Two recessive
cancer-predisposition syndromes, xeroderma pigmentosum group A (XPAC)
and Fanconi anemia group C (FACC), map to the NBCCS region; and unusual,
dominant mutations in these genes have been proposed as the cause of
Gorlin syndrome. This study presents cytogenetic and molecular
characterization of germ-line deletions in one patient with a chromosome
9q22 deletion and in a second patient with a deletion of 9q22-q3l. Both
have typical features of Gorlin syndrome plus additional findings,
including mental retardation, conductive hearing loss, and failure to
thrive. That Gorlin syndrome can be caused by null mutations (deletions)
rather than by activating mutations has several implications. First, in
conjunction with previous analyses of allelic loss in tumors, this study
provides evidence that associated neoplasms arise with homozygous
inactivation of the gene. In addition, dominant mutations of the XPAC
and FACC1 genes can be ruled out as the cause of Gorlin syndrome, since
the two patients described have null mutations. Finally, phenotypic
features that show variable expression must be influenced by genetic
background, epigenetic effects, somatic mutations, or environmental
factors, since these two patients with identical alterations (deletions)
of the Gorlin syndrome gene have somewhat different manifestations of
Gorlin syndrome.
9
UI - 8738998
AU - Petrikovsky BM; Bialer MG; McLaughlin JA; Bale AE
TI -
Sonographic and DNA-based prenatal detection of Gorlin syndrome.
SO - J Ultrasound Med 1996 Jun;15(6):493-5
AD - Department of Obstetrics, North Shore University Hospital Cornell
University Medical College, Manhasset, New York.
10
UI - 10653132
AU - Levanat S; Mubrin MK; Crnic I; Situm M; Basta-Juzbasic A
TI -
Variable expression of Gorlin syndrome may reflect complexity of the
signalling pathway.
SO - Pflugers Arch 2000;439(3 Suppl):R31-3
AD - Department of Molecular Medicine, Ruder Boskovic Institute, Zagreb,
Croatia. levanat@rudjer.irb.hr
Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin syndrome is an
autosomal dominant disorder characterized by cancer predisposition and
multiple developmental defects. Syndrome related disorders have been
attributed to alterations of PTCH gene, which plays an important role in
Shh signalling pathway. Unresolved complexities of the pathway impede
understanding of mechanisms through which PTCH alterations lead to
variable phenotype expression in Gorlin syndrome patients, while the
role of chromosomal instability is not yet clear. To increase our
understanding of NBCCS, every manifestation of the syndrome and
associated genetic damage should be seriously considered. Therefore,
several atypical NBCCS cases are presented in this paper.
11
UI - 10554356
AU - Situm M; Levanat S; Crnic I; Pavelic B; Macan D; Grgurevic J;
TI -
Mubrin-Koncar M; Lipozencic J
Involvement of patched (PTCH) gene in Gorlin syndrome and related
disorders: three family cases.
SO - Croat Med J 1999 Dec;40(4):533-8
AD - Department of Molecular Medicine, Rudjer Boskovi Institute, Bijenicka
54, 10000 Zagreb, Croatia.
AIM: To find genetic alterations in PTC or other genes of the Shh/PTCH
pathway in tumorous and non- tumorous samples from three families and to
correlate them with the varying expression of disorders in presented
nevoid basal cell carcinoma syndrome (NBCCS) phenotypes. METHOD: DNA was
extracted from archival paraffin-embedded tissues, tumor tissue or
peripheral blood leukocytes, and the loss of heterozygosity (LOH) and
single strand conformational polymorphism analysis was performed using
PCR with primers for polymorphic 9q22.3 markers (D9S196, D9S287, D9S180,
D9S127); PTCH exons 3, 6, 8, 13, 15, 16; and smo (smoothened) exon 1.
G-banding tecnique was used for cytogenetic analysis of the peripheral
blood lymphocytes. RESULTS: We found a LOH for PTCH in several cases and
variability in smo in one case. In one case NBCCS could reasonably be
ascribed to hemizygous PTCH inactivation, while in other two families
this typical correlation between the syndrome phenotype and the observed
genetic alterations could not been established. CONCLUSIONS: Further
analysis of relatively sparse cases of NBCCS is needed before the
symptoms of the syndrome could be convincingly explained by genetic
alterations in the Shh/PTCH signalling pathway.
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