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Abramson Cancer CenterNCI CANCERLIT® Search: Familial Adenomatous Polyposis - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- Direct analysis for familial adenomatous polyposis mutations.
- Flies in the colon.
- Peutz-Jeghers syndrome.
- Molecular markers of heterogeneity in colorectal cancers and adenomas.
- Primary chemoprevention of familial adenomatous polyposis with sulindac.
- Cyclooxygenase inhibition in cancer--a blind alley or a new therapeutic reality?
- Different familial adenomatous polyposis phenotypes resulting from deletions of the entire APC exon 15.
- Expression of COX-2 and Wnt pathway genes in adenomas of familial adenomatous polyposis patients treated with meloxicam.
- Challenge in the differentiation between attenuated familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer: case report
- Genetic characterisation of patients with multiple colonic polyps.
- Molecular diagnosis of familial adenomatous polyposis (FAP): genotyping of adenomatous polyposis coli (APC) alleles by MALDI-TOF mass
- APC as a checkpoint gene: the beginning or the end?
- Top down or bottom up? Competing management structures in the morphogenesis of colorectal neoplasms.
- Explaining variation in familial adenomatous polyposis: relationship between genotype and phenotype and evidence for modifier genes.
Table of Contents
1
UI - 11876475
AU - Powell SM
TI -
Direct analysis for familial adenomatous polyposis mutations.
SO - Mol Biotechnol 2002 Feb;20(2):197-207
AD - Division of Gastroenterology, University of Virginia Health System,
Charlottesville 22908, USA. smp8n@virginia.edu
The spectrum of disease causing mutations is immense. It just so happens
that the overwhelming majority of genetic alterations in the APC gene
with leads to adenomatous polyposis coli generate truncated gene
products. This observation lead to the development of the in vitro
synthesis protein assay (protein truncation test) which is a sensitive
method to detect these truncated gene products from patient samples.
This article describes the assay to detect truncated proteins for the
APC gene, which can also be applied to other disease causing genetic
alterations which commonly lead to truncations such in HNPCC, von
Hippel-Lindau, osteogenesis imperfecta, retinoblastoma, BCRAI,
beta-thalassemia, hemophilia B, Duchenene and Becker muscular dystrophy.
2
UI - 12096154
AU - Berry C
TI -
Flies in the colon.
SO - QJM 2002 Jul;95(7):487-8
3
UI - 10710046
AU - McGarrity TJ; Kulin HE; Zaino RJ
TI -
Peutz-Jeghers syndrome.
SO - Am J Gastroenterol 2000 Mar;95(3):596-604
AD - Department of Medicine, The Milton S. Hershey Medical Center, The
Pennsylvania State University College of Medicine, Hershey 17033-0850,
USA.
Peutz-Jeghers syndrome (PJS) is an unusual polyposis syndrome that has
enjoyed a rich and somewhat confusing history. Mucocutaneous
pigmentation and diffuse gastrointestinal hamartomas are the hallmark
features of this autosomal dominant inherited condition. Peutz-Jeghers
syndrome is now also recognized as a cancer predisposition syndrome. In
this review, we highlight the historical aspects of PJS polyposis with
special emphasis on its extraintestinal manifestations, particularly
genital tract tumors. A PJS management scheme for clinicians is
included.
4
UI - 11917214
AU - Piard F; Chapusot C; Ecarnot-Laubriet A; Ponnelle T; Martin L
TI -
Molecular markers of heterogeneity in colorectal cancers and adenomas.
SO - Eur J Cancer Prev 2002 Feb;11(1):85-97
AD - Service d'Anatomopathologie, Faculte de Medecine BP 87900, F-21079
Dijon, France. francoise.pinard@u-bourgogne.fr
5
UI - 11932472
AU - Giardiello FM; Yang VW; Hylind LM; Krush AJ; Petersen GM; Trimbath JD;
TI -
Piantadosi S; Garrett E; Geiman DE; Hubbard W; Offerhaus GJ; Hamilton SR
Primary chemoprevention of familial adenomatous polyposis with sulindac.
SO - N Engl J Med 2002 Apr 4;346(14):1054-9
AD - Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, USA.
BACKGROUND: Familial adenomatous polyposis is caused by a germ-line
mutation in the adenomatous polyposis coli gene and is characterized by
the development of hundreds of colorectal adenomas and, eventually,
colorectal cancer. Nonsteroidal antiinflammatory drugs can cause
regression of adenomas, but whether they can prevent adenomas is
unknown. METHODS: We conducted a randomized, double-blind,
placebo-controlled study of 41 young subjects (age range, 8 to 25 years)
who were genotypically affected with familial adenomatous polyposis but
phenotypically unaffected. The subjects received either 75 or 150 mg of
sulindac orally twice a day or identical-appearing placebo tablets for
48 months. The number and size of new adenomas and side effects of
therapy were evaluated every four months for four years, and the levels
of five major prostaglandins were serially measured in biopsy specimens
of normal-appearing colorectal mucosa. RESULTS: After four years of
treatment, the average rate of compliance exceeded 76 percent in the
sulindac group, and mucosal prostaglandin levels were lower in this
group than in the placebo group. During the course of the study,
adenomas developed in 9 of 21 subjects (43 percent) in the sulindac
group and 11 of 20 subjects in the placebo group (55 percent) (P=0.54).
There were no significant differences in the mean number (P=0.69) or
size (P=0.17) of polyps between the groups. Sulindac did not slow the
development of adenomas, according to an evaluation involving linear
longitudinal methods. CONCLUSIONS: Standard doses of sulindac did not
prevent the development of adenomas in subjects with familial
adenomatous polyposis.
6
UI - 11932478
AU - Chau I; Cunningham D
TI -
Cyclooxygenase inhibition in cancer--a blind alley or a new therapeutic
reality?
SO - N Engl J Med 2002 Apr 4;346(14):1085-7
7
UI - 12136240
AU - Su LK; Kohlmann W; Ward PA; Lynch PM
TI -
Different familial adenomatous polyposis phenotypes resulting from
deletions of the entire APC exon 15.
SO - Hum Genet 2002 Jul;111(1):88-95
AD - Department of Molecular and Cellular Oncology, Box 79, The University of
Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston
77030, USA. lsu@mdanderson.org
Germline mutations of the adenomatous polyposis coli ( APC) gene cause
familial adenomatous polyposis (FAP), an autosomal, dominantly inherited
disease that predisposes patients to colorectal cancer. The APC gene is
composed of 15 coding exons and encodes an open reading frame of 8.5 kb.
The 3' 6.5 kb of the APCopen reading frame is encoded by a single exon,
exon 15. Most identified APC mutations are at the 5' half of the APC
open reading frame and are nucleotide substitutions and small deletions
or insertions that result in truncation of the APC protein. Very few
well-characterized gross alterations of APC have been reported. Patients
with FAP typically develop hundreds to thousands of colorectal tumors
beginning in their adolescence. A subgroup of patients with FAP who
develop fewer tumors at an older age have what is called attenuated FAP
(AFAP). Accumulating evidence indicates that patients carrying germline
APC mutations in the first four coding exons, in the alternatively
spliced region of exon 9, or in the 3' half of the coding region usually
develop AFAP. We characterized two germline APC alterations that deleted
the entire APC exon 15 as the result of 56-kb and 73-kb deletions at the
APC locus. A surprising finding was that one proband had the typical FAP
phenotype, whereas the other had a phenotype consistent with that of
AFAP.
8
UI - 12174906
AU - Dobbie Z; Muller PY; Heinimann K; Albrecht C; D'Orazio D; Bendik I;
TI -
Muller H; Bauerfeind P
Expression of COX-2 and Wnt pathway genes in adenomas of familial
adenomatous polyposis patients treated with meloxicam.
SO - Anticancer Res 2002 Jul-Aug;22(4):2215-20
AD - Division of Medical Genetics, University Clinics, Basel, Switzerland.
BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal,
dominantly inherited predisposition to colorectal cancer caused by
germline mutations within the adenomatous polyposis coli (APC) gene, a
key member of the Wnt signalling pathway. A new class of non-steroidal
anti-inflammatory drugs (NSAIDs), the specific cyclooxygenase 2 (COX-2)
inhibitors, have recently been applied for the treatment of FAP
patients. PATIENTS AND METHODS: The expressions of the Wnt members and
targets APC, c-myc, cyclin D1 and COX-2, as measured by real-time
quantitative RT-PCR, have been evaluated in fresh samples of normal
colorectal mucosa and matched adenoma tissue of six unrelated FAP
patients before and after treatment with meloxicam. RESULTS: A
significant up-regulation of COX-2 in adenomas after treatment with
meloxicam was found. Furthermore, in adenomas, a down-regulation of APC
after treatment and a tight correlation of the expressions of the two
Wnt targets, c-myc and cyclin D1, in both stages of treatment were
observed. CONCLUSION: A feedback loop mediated by the peroxisome
proliferator-activated receptor (PPAR) gamma is discussed as being
responsible for the up-regulation of COX-2
9
UI - 12135043
AU - Cao Y; Pieretti M; Marshall J; Khattar NH; Chen B; Kam-Morgan L; Lynch H
TI -
Challenge in the differentiation between attenuated familial adenomatous
polyposis and hereditary nonpolyposis colorectal cancer: case report
with review of the literature.
SO - Am J Gastroenterol 2002 Jul;97(7):1822-7
AD - Department of Internal Medicine, St Luke's Hospital, Chesterfield,
Missouri 63017, USA.
The clinical differentiation between hereditary nonpolyposis colorectal
cancer (HNPCC) and attenuated familial adenomatous polyposis (AFAP) is
very difficult. The 62-yr-old proband presented with duodenal
adenocarcinoma. His history of subtotal colectomy for colon cancer, the
rarity of duodenal adenocarcinoma in the general population, and his
family history of colon cancer made us suspect that he might have FAP.
We investigated this family by obtaining medical records and performing
gene analysis. The proband had only 10 adenomatous colon polyps when he
underwent subtotal colectomy for the cancer, so classic FAP was
excluded. His family history included rectal cancer in his brother at 69
yr of age, colon cancer in his mother at 75 yr, and colon cancer in one
maternal cousin at 42 yr. Three months after we started to study this
family, the proband's 32-yr-old son presented with rectal cancer. His
family fulfilled the Amsterdam criteria for HNPCC, but AFAP could not be
excluded. Upon gene testing, the proband was negative for APC gene
germline mutation, which made AFAP highly unlikely. Moreover, high
microsatellite instability (MSI) was detected in his adenomas and cancer
tissues. The fulfillment of Amsterdam criteria, the exclusion of FAP and
AFAP, and the high MSI established the diagnosis of HNPCC in this
family. We also summarize the differences between FAP, AFAP, and HNPCC;
extend the graphic description of the MSI mechanism; and propose a
diagnostic strategy for HNPCC.
10
UI - 11950865
AU - Albuquerque C; Cravo M; Cruz C; Lage P; Chaves P; Fidalgo P; Suspiro A;
TI -
Nobre Leitao C
Genetic characterisation of patients with multiple colonic polyps.
SO - J Med Genet 2002 Apr;39(4):297-302
11
UI - 11983341
AU - Bonk T; Humeny A; Sutter C; Gebert J; von Knebel Doeberitz M; Becker CM
TI -
Molecular diagnosis of familial adenomatous polyposis (FAP): genotyping
of adenomatous polyposis coli (APC) alleles by MALDI-TOF mass
spectrometry.
SO - Clin Biochem 2002 Mar;35(2):87-92
AD - Institut fur Biochemie, Emil-Fischer-Zentrum, Universitat
Erlangen-Nurnberg, Fahrstrasse 17 D-91054, Erlangen, Germany.
OBJECTIVES: Familial adenomatous polyposis (FAP) is an autosomal
dominantly inherited colorectal cancer predisposition syndrome caused by
germ line mutations in the adenomatous polyposis coli gene (APC). For
prophylactic colectomy, timely identification of patients at risk is
urgent. Here, matrix assisted laser desorption ionization - time of
flight - mass spectrometry (MALDI-TOF-MS) genotyping is offered for an
efficient molecular diagnosis of APC germline mutations. DESIGN AND
METHODS: The four most frequent APC germ line mutations (three
deletions, one point mutation) were genotyped by allele specific
elongation and termination of extension primers. The extension products
generated were analyzed by MALDI-TOF-MS. RESULTS: Following PCR
amplification and allele specific primer extension reactions
MALDI-TOF-MS allowed the unambiguous identification of informative
nucleic acid fragments corresponding to distinct genotypes or mutants
even in duplex assays. Results were confirmed by DNA-sequencing.
CONCLUSIONS: Due to its high molecular resolution and accuracy, this
method is highly suitable as an alternative for clinical APC genotyping.
12
UI - 12198717
AU - Yang VW
TI -
APC as a checkpoint gene: the beginning or the end?
SO - Gastroenterology 2002 Sep;123(3):935-9
13
UI - 12171945
AU - Wright NA; Poulsom R
TI -
Top down or bottom up? Competing management structures in the
morphogenesis of colorectal neoplasms.
SO - Gut 2002 Sep;51(3):306-8
AD - Histopathology Unit, Cancer Research UK, 44 Lincoln's Inn Fields, London
WC2A 3PX, UK. warden@qmul.ac.uk
14
UI - 12171967
AU - Crabtree MD; Tomlinson IP; Hodgson SV; Neale K; Phillips RK; Houlston RS
TI -
Explaining variation in familial adenomatous polyposis: relationship
between genotype and phenotype and evidence for modifier genes.
SO - Gut 2002 Sep;51(3):420-3
AD - Molecular and Population Genetics Laboratory, Imperial Cancer Research
Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
m.crabtree@icrf.icnet.uk
BACKGROUND: Familial adenomatous polyposis (FAP) is characterised by
variable phenotypic expression. Part of this is attributable to a
relationship between APC genotype and phenotype but there remains
significant intrafamilial variation. In the Min mouse model of FAP,
differences in the severity of gastrointestinal polyposis result from
the action of modifier genes. AIMS: To determine whether phenotypic
variation in human FAP has an inherited component consistent with the
action of modifier genes. METHOD: We systematically examined polyp
numbers in colectomy specimens from patients with classical FAP.
Variation both between and within families was analysed. Formal
modelling of the segregation of disease severity in families was
performed RESULTS: There was strong evidence for a relationship between
site of mutation and the number of colorectal polyps, with germline
mutations in the "cluster region" causing the most severe disease and
those with mutations between codons 1020 and 1169 having the mildest
disease. In addition to this genotype-phenotype relationship, we found
evidence for non-APC linked genetic modifiers of disease expression.
First degree relatives had more similar polyp counts than more distant
relatives. Formal modelling of the segregation of disease severity in
families revealed further evidence for the action of modifier genes,
with a best fit to a mixed model of inheritance. CONCLUSION: Our data
provide good evidence to support the hypothesis that modifier genes
influence the severity of FAP in humans.
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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