Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC). Our purpose is to describe three extended HNPCC families, each of which manifests novel germline mutations in Uruguay, a small country that is a study model for cancer investigation given its high cancer incidence and mortality rate. This is a study of three extended HNPCC families in which extensive genealogic information, medical history, and pathology findings are critically reviewed. DNA testing was performed for evidence of HNPCC mutations. The findings reveal three novel germline mutations, namely MLH1, with a deletion resulting in a frameshift and a premature stop codon (codon 228) in one of the families; in the second family, MSH2 exon 1, codon 61 at nucleotide 181, which results in immediate stop of translation; and in the third family, a mutation in MSH2 at exon 3: the amino acid at nucleotide 530, codon 117, causing a frameshift and a premature stop codon eight base pairs later. We conclude that it is important to study HNPCC mismatch repair genes because of emerging evidence for genotypic and phenotypic heterogeneity, which will harbor the potential to eventually translate this knowledge into specific screening and management protocols. Future projections for such mutations could even contribute to the emergence of molecular-based designer drugs developed through advances in genomics, proteomics, high-throughput screening, and bioinformatics, which would be effective therapeutically for these high-cancer risk patients.
| Original language | English |
|---|---|
| Pages (from-to) | 13-20 |
| Number of pages | 8 |
| Journal | Cancer Genetics and Cytogenetics |
| Volume | 142 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 1 2003 |
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All Science Journal Classification (ASJC) codes
- Cancer Research
- Genetics
- Molecular Biology
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Three new mutations in hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay. / Sarroca, Carlos; Peltomäki, Päivi; Alfano, Nora; Tedesco, Gladys; Della Valle, Adriana; Dominguez, Alejandra; Lynch, Henry T.
In: Cancer Genetics and Cytogenetics, Vol. 142, No. 1, 01.04.2003, p. 13-20.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Three new mutations in hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay
AU - Sarroca, Carlos
AU - Peltomäki, Päivi
AU - Alfano, Nora
AU - Tedesco, Gladys
AU - Della Valle, Adriana
AU - Dominguez, Alejandra
AU - Lynch, Henry T.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC). Our purpose is to describe three extended HNPCC families, each of which manifests novel germline mutations in Uruguay, a small country that is a study model for cancer investigation given its high cancer incidence and mortality rate. This is a study of three extended HNPCC families in which extensive genealogic information, medical history, and pathology findings are critically reviewed. DNA testing was performed for evidence of HNPCC mutations. The findings reveal three novel germline mutations, namely MLH1, with a deletion resulting in a frameshift and a premature stop codon (codon 228) in one of the families; in the second family, MSH2 exon 1, codon 61 at nucleotide 181, which results in immediate stop of translation; and in the third family, a mutation in MSH2 at exon 3: the amino acid at nucleotide 530, codon 117, causing a frameshift and a premature stop codon eight base pairs later. We conclude that it is important to study HNPCC mismatch repair genes because of emerging evidence for genotypic and phenotypic heterogeneity, which will harbor the potential to eventually translate this knowledge into specific screening and management protocols. Future projections for such mutations could even contribute to the emergence of molecular-based designer drugs developed through advances in genomics, proteomics, high-throughput screening, and bioinformatics, which would be effective therapeutically for these high-cancer risk patients.
AB - Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common hereditary form of colorectal cancer (CRC). Our purpose is to describe three extended HNPCC families, each of which manifests novel germline mutations in Uruguay, a small country that is a study model for cancer investigation given its high cancer incidence and mortality rate. This is a study of three extended HNPCC families in which extensive genealogic information, medical history, and pathology findings are critically reviewed. DNA testing was performed for evidence of HNPCC mutations. The findings reveal three novel germline mutations, namely MLH1, with a deletion resulting in a frameshift and a premature stop codon (codon 228) in one of the families; in the second family, MSH2 exon 1, codon 61 at nucleotide 181, which results in immediate stop of translation; and in the third family, a mutation in MSH2 at exon 3: the amino acid at nucleotide 530, codon 117, causing a frameshift and a premature stop codon eight base pairs later. We conclude that it is important to study HNPCC mismatch repair genes because of emerging evidence for genotypic and phenotypic heterogeneity, which will harbor the potential to eventually translate this knowledge into specific screening and management protocols. Future projections for such mutations could even contribute to the emergence of molecular-based designer drugs developed through advances in genomics, proteomics, high-throughput screening, and bioinformatics, which would be effective therapeutically for these high-cancer risk patients.
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U2 - 10.1016/S0165-4608(02)00766-5
DO - 10.1016/S0165-4608(02)00766-5
M3 - Article
VL - 142
SP - 13
EP - 20
JO - Cancer Genetics and Cytogenetics
JF - Cancer Genetics and Cytogenetics
SN - 0165-4608
IS - 1
ER -