Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.

Planck, Maria; Halvarsson, Britta; Pålsson, Eva; Hallén, Magnus; Ekelund, Mats; Pålsson, Birger; Baldetorp, Bo; Nilbert, Mef

Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.

Mark

Planck, Maria ^LU ; Halvarsson, Britta ^LU ; Pålsson, Eva ^LU ; Hallén, Magnus ^LU ; Ekelund, Mats ^LU ; Pålsson, Birger ^LU ; Baldetorp, Bo ^LU and Nilbert, Mef ^LU (2002) In Cancer Genetics and Cytogenetics 134(1). p.46-54

Abstract: The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of... (More); The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of the primary tumor and in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII) showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR) displayed alterations in some tumor regions but not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7 and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor suggests that these phenomena may act together in HNPCC tumorigenesis. Furthermore, the observed intratumoral heterogeneity of mutations in coding repeats implies these changes occur late in tumorigenesis and, thus, probably play a role in tumor progression rather than initiation. (Less)

Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/108063

author

Planck, Maria ^LU ; Halvarsson, Britta ^LU ; Pålsson, Eva ^LU ; Hallén, Magnus ^LU ; Ekelund, Mats ^LU ; Pålsson, Birger ^LU ; Baldetorp, Bo ^LU and Nilbert, Mef ^LU

organization

publishing date

2002

type

Contribution to journal

publication status

published

subject

Cancer and Oncology

keywords

DNA Mutational Analysis, Neoplasm : chemistry, DNA, Neoplasm : genetics, Female, Flow Cytometry, Genetic Heterogeneity, Genetic Predisposition to Disease : genetics, Human, In Situ Hybridization, Fluorescence, Karyotyping, Microsatellite Repeats, Mutation, Neoplasm Proteins : genetics, Nucleic Acid : genetics, Repetitive Sequences, Ploidies, Support, Non-U.S. Gov't, Hereditary Nonpolyposis : pathology, Colorectal Neoplasms, Hereditary Nonpolyposis : genetics, Colonic Neoplasms : pathology, Colonic Neoplasms : genetics, Chromosome Aberrations

in

Cancer Genetics and Cytogenetics

volume

134

issue

1

pages

46 - 54

publisher

Elsevier

external identifiers

pmid:11996796
wos:000175165700010
scopus:0036538849

ISSN

0165-4608

DOI

10.1016/S0165-4608(01)00587-8

language

English

LU publication?

yes

additional info

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Surgery (Lund) (013009000), Pathology, (Lund) (013030000), Division of Clinical Genetics (013022003), Oncology, MV (013035000), Surgery Research Unit (013242220)

id

d4235d88-1939-40ab-905e-8f78fa9c9904 (old id 108063)

alternative location

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11996796&dopt=Abstract

date added to LUP

2016-04-01 16:49:02

date last changed

2022-01-28 22:23:09

@article{d4235d88-1939-40ab-905e-8f78fa9c9904,
  abstract     = {{The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of the primary tumor and in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII) showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR) displayed alterations in some tumor regions but not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7 and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor suggests that these phenomena may act together in HNPCC tumorigenesis. Furthermore, the observed intratumoral heterogeneity of mutations in coding repeats implies these changes occur late in tumorigenesis and, thus, probably play a role in tumor progression rather than initiation.}},
  author       = {{Planck, Maria and Halvarsson, Britta and Pålsson, Eva and Hallén, Magnus and Ekelund, Mats and Pålsson, Birger and Baldetorp, Bo and Nilbert, Mef}},
  issn         = {{0165-4608}},
  keywords     = {{DNA Mutational Analysis; Neoplasm : chemistry; DNA; Neoplasm : genetics; Female; Flow Cytometry; Genetic Heterogeneity; Genetic Predisposition to Disease : genetics; Human; In Situ Hybridization; Fluorescence; Karyotyping; Microsatellite Repeats; Mutation; Neoplasm Proteins : genetics; Nucleic Acid : genetics; Repetitive Sequences; Ploidies; Support; Non-U.S. Gov't; Hereditary Nonpolyposis : pathology; Colorectal Neoplasms; Hereditary Nonpolyposis : genetics; Colonic Neoplasms : pathology; Colonic Neoplasms : genetics; Chromosome Aberrations}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{46--54}},
  publisher    = {{Elsevier}},
  series       = {{Cancer Genetics and Cytogenetics}},
  title        = {{Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.}},
  url          = {{http://dx.doi.org/10.1016/S0165-4608(01)00587-8}},
  doi          = {{10.1016/S0165-4608(01)00587-8}},
  volume       = {{134}},
  year         = {{2002}},
}

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Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.