- Cancer Types
Information about risk, prevention, screening, symptoms, diagnosis, treatment, and support for all cancers Cancer A to Z - Cancer Treatment
Cancer Treatment
Information about cancer treatment, including surgery, chemotherapy, radiation therapy, clinical trials, proton therapy, complementary medicine, and cutting edge technologies.
- Risk and Prevention
- Cancer Drugs
- Support
Support
Ways for cancer patients and caregivers to cope with cancer, side effects, nutrition, general cancer support issues, grief/end of life issues, and shared survivor's experiences.
- Healthcare Professionals
- Clinical Trials
My Patient Treatment Binder
OncoLink Blogs
What's My Cancer Risk?
OncoPilot: Navigating Your Cancer Journey
Community Events Calendar
OncoLink eNews
Abramson Cancer CenterNCI CANCERLIT® Search: Non-polyposis Colon Cancer, Hereditary - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- Hereditary non-polyposis colorectal cancer (HNPCC): phenotype-genotype correlation between patients with and without identified mutation.
- Missense mismatch repair gene alterations, microsatellite instability, and hereditary nonpolyposis colorectal cancer.
- A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of
- Current status of genetic testing for colorectal cancer susceptibility.
- [Glioblastoma multiforme as a manifestation of Turcot syndrome]
- Debate surges over the origins of genomic defects in cancer.
- Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer.
- A hMLH1 genomic mutation and associated novel mRNA defects in a hereditary non-polyposis colorectal cancer family.
- DNA mismatch repair defects: role in colorectal carcinogenesis.
- Genetic insights into familial cancers-- update and recent discoveries.
Table of Contents
1
UI - 12112654
AU - Bisgaard ML; Jager AC; Myrhoj T; Bernstein I; Nielsen FC
TI -
Hereditary non-polyposis colorectal cancer (HNPCC): phenotype-genotype
correlation between patients with and without identified mutation.
SO - Hum Mutat 2002 Jul;20(1):20-7
AD - Department of Clinical Biochemistry, Rigshospitalet, Copenhagen,
Denmark. mls.bisgaard@get2net.dk
Affected members of hereditary non-polyposis colorectal cancer (HNPCC)
families develop colorectal cancer at an early age (mean 45 yr) and
frequently get extracolonic cancers particularly in the uterus, urinary
tract, and small intestine. They have a high risk of developing more
than one primary colorectal cancer if not treated with subtotal
colectomy at first operation and have more frequent right-sided colon
cancers and less frequent rectum cancers, compared to patients with
sporadic colorectal cancer. We have screened 31 families fulfilling the
Amsterdam criteria and 54 families with a colorectal cancer clustering
but not fulfilling the Amsterdam criteria for mutations in MLH1 and MSH2
by direct sequencing, and detected a mutation in 61% of the Amsterdam
positive families but only in 15% of the Amsterdam negative families.
Genotype-phenotype correlation was compared between 141 affected
individuals with an identified mutation and 78 affected individuals from
Amsterdam positive families in which a mutation was not identifiable in
MLH1 or MSH2. In the affected persons with identified mutations, all
expected phenotypic traits were represented, whereas affected persons in
whom no mutation was detected fell into two clearly distinguishable
subgroups. The minor subgroup, in which no mutation was identified,
generally had the same characteristics as found in affected persons with
identified mutations. The major subgroup differed significantly in
clinical features and exhibited phenotypic traits similar to those found
in late-onset families, including abundance of rectal cancer, few
HNPCC-related cancers, lower frequency of multiple colorectal cancers,
and later age at onset. Finally, for six missense mutations and one
single codon deletion, the pathogenic potential was evaluated by domain
localization, lod score calculation or segregation analysis when
possible, and mutation-induced biochemical change. The results indicate
that the majority of missense mutations are pathogenic, although further
characterization by functional assays is necessary before implementation
in predictive testing programs. Copyright 2002 Wiley-Liss, Inc.
2
UI - 12118033
AU - Samowitz WS; Slattery ML
TI -
Missense mismatch repair gene alterations, microsatellite instability,
and hereditary nonpolyposis colorectal cancer.
SO - J Clin Oncol 2002 Jul 15;20(14):3178; discussion 3178-9
3
UI - 12124320
AU - Gazzoli I; Loda M; Garber J; Syngal S; Kolodner RD
TI -
A hereditary nonpolyposis colorectal carcinoma case associated with
hypermethylation of the MLH1 gene in normal tissue and loss of
heterozygosity of the unmethylated allele in the resulting
microsatellite instability-high tumor.
SO - Cancer Res 2002 Jul 15;62(14):3925-8
AD - Ludwig Institute of Cancer Research, University of California San Diego
School of Medicine, La Jolla, California 92093, USA. igazzoli@ucsd.edu
Fourteen suspected hereditary nonpolyposis colorectal carcinoma cases
with microsatellite unstable(microsatellite instability-high; MSI-H)
tumors but no germ-line MSH2, MSH6, or MLH1 mutations were examined for
hypermethylation of CpG sites in the critical promoter region of MLH1.
The methylation patterns were determined using methylation-specific PCR
and by sequence analysis of sodium bisulfite-treated genomic DNA. In one
case, DNA hypermethylation of one allele was detected in DNA isolated
from blood. In the MSI-H tumor from this case, the unmethylated MLH1
allele was eliminated by loss of heterozygosity, and the methylated
allele was retained. This biallelic inactivation resulted in loss of
expression of MLH1 in the tumor as confirmed by immunohistochemistry.
These results suggest a novel mode of germ-line inactivation of a cancer
susceptibility gene.
4
UI - 11866134
AU - Solomon CH; Pho LN; Burt RW
TI -
Current status of genetic testing for colorectal cancer susceptibility.
SO - Oncology (Huntingt) 2002 Feb;16(2):161-71; discussion 176, 179-80
AD - Division of Gastroenterology, Huntsman Cancer Institute at the
University of Utah, Salt Lake City 84112, USA.
Over 130,000 new cases of colon cancer are diagnosed annually.
Approximately 20% to 30% of these are attributable to familial risk, and
3% to 5% belong to a hereditary colorectal cancer predisposition
syndrome. Recent discoveries of the genes responsiblefor the inherited
colorectal cancer conditions have expanded the field of commercial
genetic testing. Health-care providers who use genetic testing in
clinical practice are aware of the benefits that genetic testing can
confer on screening, prevention, and treatment options for patients with
a personal and/or family history of colon cancer. When genetic test
results are correctly interpreted, the information they provide can
offer medical guidance for the entire family. The psychological impact,
however, of presymptomatic testing can be multifaceted. There are
unprecedented benefits but also complex issues surrounding genetic
testing. For these reasons, the practice of offering genetic testing to
individuals at high risk for colon cancer is heavily fortified with
guidelines and recommendations. This review covers the current
availability and limitations of genetic testing for inherited colorectal
cancer syndromes and focuses on guidelines that address the
psychological, ethical, and social concerns stemming from genetic
testing.
5
UI - 11975096
AU - Grips E; Wentzensen N; Sutter C; Sedlaczek O; Gebert J; Weigel R;
TI -
Schwartz A; von Knebel-Doeberitz M; Hennerici M
[Glioblastoma multiforme as a manifestation of Turcot syndrome]
SO - Nervenarzt 2002 Feb;73(2):177-82
AD - Neurologische Universitatsklinik Mannheim, Ruprecht-Karls-Universitat
Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim.
Turcot's syndrome, clinically characterized by the coincident occurrence
of primary tumors of the colon and the central nervous system, can
genetically be divided into two syndromes: familial adenomatous
polyposis (FAP) and hereditary nonpolyposis colon carcinoma (HNPCC). In
the present case, a 60-year-old patient with glioblastoma multiforme and
a history of hereditary malignomas is described as an example of a
HNPCC-associated Turcot's syndrome. New molecular biological methods and
results give deeper insight into clinical syndromes, and the better
understanding improves diagnostics, therapy, and outcome estimations,
even in rare diseases. In the present case, a new germinal mutation
could be identified.
6
UI - 12142522
AU - Marx J
TI -
Debate surges over the origins of genomic defects in cancer.
SO - Science 2002 Jul 26;297(5581):544-6
7
UI - 11788565
AU - Lindgren G; Liljegren A; Jaramillo E; Rubio C; Lindblom A
TI -
Adenoma prevalence and cancer risk in familial non-polyposis colorectal
cancer.
SO - Gut 2002 Feb;50(2):228-34
AD - Department of Clinical Genetics, Karolinska Hospital, S 171 76
Stockholm, Sweden.
BACKGROUND AND AIMS: Polypectomy in the colon has been shown to prevent
colorectal cancer in both the general population and in familial
colorectal cancer. Individuals with a family history of colorectal
cancer have an increased risk of the disease. Over a period of 10 years,
304 subjects at risk were included in ongoing surveillance with regular
colonoscopies. To compile the medical findings and experience generated
during this period, a retrospective cross sectional study was performed.
SUBJECTS: Subjects were classified into three family groups: families
with hereditary non-polyposis colorectal cancer (HNPCC); families with
hereditary colorectal cancer (HCC, non-Lynch syndrome); and a third
group of families with only empirical risk estimates based on a family
history of two close relatives (TCR) with colorectal cancer. METHODS:
The risk population was studied with regard to age at onset, prevalence,
number, cancer risk, size, dysplasia, and distribution of adenomas. A
comparison was made within the family groups and with a reference group
representing the general population. RESULTS: In total, 195 adenomas and
six cancers were detected among 85 individuals. The relative risk of
having an adenoma in the whole risk population compared with the general
population was 2.6. Subjects from TCR families had most adenomas and
HNPCC subjects had the least. A shift from proximal adenomas to distal
carcinomas in families with HCC and TCR suggested a higher cancer risk
in distal adenomas in these syndromes. HNPCC families showed a younger
age at onset and adenomas with a higher degree of dysplasia. In HNPCC,
there was a similar localisation of adenomas and carcinomas, suggesting
a high risk of cancer in all adenomas. CONCLUSIONS: There was clear
overrepresentation of adenomas in all three family types compared with
the reference population. In HNPCC, we found earlier onset of adenomas
and faster progression to cancer. Families with HCC, and even more so
TCR subjects, had a later onset and lower risk of cancer from proximal
adenomas. Based on these results, surveillance protocols in Sweden have
been revised.
8
UI - 12052501
AU - Tanko Q; Franklin B; Lynch H; Knezetic J
TI -
A hMLH1 genomic mutation and associated novel mRNA defects in a
hereditary non-polyposis colorectal cancer family.
SO - Mutat Res 2002 Jun 19;503(1-2):37-42
AD - School of Medicine, Department of Biomedical Sciences, Creighton
University, 2500 California Plaza, Omaha, NE 68178, USA.
Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome I,
is responsible for as high as 10% of all colorectal cancers (CRCs) newly
diagnosed in any given year. This disorder has an autosomal dominant
inheritance pattern and is almost fully penetrant (>85%). It occurs when
there is a mutation in any one of six mismatch repair genes: hMLH1,
hMSH2, hPMS1, hPMS2, hMSH3 and hMSH6. Mutations in these genes allow
mistakes in tumor suppressor genes and oncogenes to accumulate which
eventually leads to cancer. The founder of an HNPCC family in the
Creighton University Hereditary Cancer Institute database was known to
produce truncated hMLH1 protein, a product of one of the aforementioned
mismatch repair genes. Lymphoblasts were isolated from ten members of
this HNPCC family (six affected and four unaffected) and two persons
from outside this family (both unaffected controls). RNA and DNA were
purified from these lymphoblasts which had been transformed by the
Epstein-Barr virus (EBV). The hypothesis was that a mutation in the
hMLH1 gene perpetuated defects in its mRNA and functional protein. hMLH1
RNA transcripts were detected in reverse transcriptase polymerase chain
reactions (RT-PCR) whereby total poly A(+) RNA was converted to a
complementary DNA (cDNA), amplified using hMLH1 specific primers,
purified and cycle sequenced. Likewise, DNA was employed as template for
PCR amplification of hMLH1 exons; PCR products were then directly cycle
sequenced. Affected family members were found to produce hMLH1 mRNA
lacking exons 6 and 7 (and wild-type mRNA). A splicing mutation at
546--2 (two bases 5' to exon 7) was located in the genomic DNA samples
from the six family members with the HNPCC phenotype. This mutation
caused deletion of exon 7 from the mRNA. None of the four unaffected
family members or the two unaffected persons outside of this family had
the above defects in their hMLH1 mRNA and DNA.
9
UI - 11900875
AU - Jacob S; Praz F
TI -
DNA mismatch repair defects: role in colorectal carcinogenesis.
SO - Biochimie 2002 Jan;84(1):27-47
AD - CNRS, Unite Propre de Recherches 2169, Genetic Instability and Cancer,
7, rue Guy-Moquet, 94800 Villejuif, France.
The inactivation of the DNA mismah repair (MMR) system, which is
associated with the predisposition to the hereditary non-polyposis
colorectal cancer (HNPCC), has also been documented in nearly 20% of the
sporadic colorectal cancers. These tumors are characterized by a high
frequency of microsatellite instability (MSI(+) phenotype), resulting
from the accumulation of small insertions or deletions that frequently
arise during replication of these short repeated sequences. A germline
mutation of one of the two major MMR genes (hMSH2 or hMLH1) is found in
half to two-thirds of the patients with HNPCC, whereas in sporadic cases
hypermethylation of the hMLH1 promoter is the major cause of the MMR
defect. Germline mutations in hMSH6 are rare and rather confer
predisposition to late-onset familial colorectal cancer, and frequent
extracolonic tumors. Yet, the genetic background of a number of HNPCC
patients remains unexplained, indicating that other genes participate in
MMR and play important roles in cancer susceptibility. The
tumor-suppressor genes that are potential targets for the MSI-driven
mutations because they contain hypermutable repeated sequences are
likely to contribute to the etiology and tissue specificity of the
MSI-associated carcinogenesis. Because the prognosis and the
chemosensitivity of the MSI(+) colorectal tumors differ from those
without instability, the determination of the MSI phenotype is expected
to improve the clinical management of patients. This review gives an
overview of various aspects of the biochemistry and genetics of the DNA
mismah repair system, with particular emphasis in its role in colorectal
carcinogenesis.
10
UI - 12175530
AU - Marsh D; Zori R
TI -
Genetic insights into familial cancers-- update and recent discoveries.
SO - Cancer Lett 2002 Jul 26;181(2):125-64
AD - Cancer Genetics, Kolling Institute of Medical Research and Department of
Molecular Medicine, The University of Sydney, Royal North Shore
Hospital, St. Leonards, NSW 2065, Sydney, Australia.
debbie_marsh@med.usyd.edu.au
While the vast majority of cancers are believed to occur sporadically,
most forms of cancer, both adult and paediatric, have a hereditary
equivalent. In the case of adult malignancies, these include hereditary
breast and ovarian cancer and syndromes such as the multiple endocrine
neoplasias types 1 and 2 characterised by specific tumours of the
endocrine gland system. In the case of paediatric malignancies, these
include syndromes such as retinoblastoma and Wilms tumour. In a little
over a single decade, we have seen a tremendous increase in the
knowledge of the primary genetic basis of many of the familial cancer
syndromes. The majority of familial syndromes are inherited as autosomal
dominant traits including hereditary colon cancer and familial malignant
melanoma, however, the genetics behind autosomal recessive disorders
such as Bloom syndrome and Fanconi anaemia are also being elucidated. A
third mode of inheritance less well understood in the setting of
familial cancer is that of imprinting recently observed in a subset of
families with inherited paraganglioma. In this review, we discuss 31
genes inherited in an autosomal dominant manner associated with 20
familial cancer syndromes. Genes inherited in an autosomal recessive
manner linked to familial cancer syndromes are also discussed. The
identification of genes associated with familial cancer syndromes has in
some families enabled a 'molecular diagnosis' that complements clinical
assessment and allows directed cancer surveillance for those individuals
determined to be at-risk of disease.
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.
Cancer Types
Bone Cancer
Brain Tumors
Breast Cancer
Carcinoid Tumors
Endocrine System Cancers
Gastrointestinal Cancers
Gynecologic Cancers
Head and Neck Cancers
Leukemia
Lung Cancers
Lymphomas
Myelomas
Pediatric Cancers
Penile Cancer
Prostate Cancer
Sarcomas
Skin Cancers
Testicular Cancer
Thyroid Cancer
Urinary Tract Cancers
OncoLink Vet
Cancer Treatment
Biologic Therapy
Bone Marrow Transplants
Chemotherapy
Clinical Trials
Complementary Medicine
Gene Therapy
General Treatment Concerns
Hormone Therapy
PDT Center
Proton Therapy
Radiation Oncology
Surgical Oncology
Targeted Therapies
Vaccine Therapies
Cancer Support
Caregivers
Hospice Care and Bereavement
Nutrition and Cancer
Sexuality & Fertility
Side Effects
Support
Survivorship
Exercise and Cancer
Cancer Resources
Cancer News
OncoLink University
Nurses' Notes
Conferences
Newly Diagnosed Patients
Causes and Prevention
Legal and Financial Information for Patients
LGBT Resources
NCI Resources
Global Resources
Cancer Resource List
Resources for Young Adults
OncoLink Media Library
OncoLink TV
Book, Music and Video Reviews
Ask the Experts
Brown Bag Chat
Tracy's Corner
About OncoLink
About OncoLink
Giving to OncoLink
Contact Information
Usage Policy
Editorial Board
How to Partner with OncoLink
Link to OncoLink
Mission Statement
