Hereditary nonpolyposis colorectal cancer and related conditions

Lucci-Cordisco, Emanuela; Zito, Ilaria; Gensini, Francesca; Genuardi, Maurizio

doi:10.1002/ajmg.a.20475

Cited by 73 publications

(44 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…15 A subtype of Muir-Torre syndrome, associated with microsatellite instability and a defective DNA mismatch repair protein system, is closely linked to the development of hereditary nonpolyposis colorectal cancer or Lynch syndrome. 16,17 A clinical diagnosis of this subtype can be made in a patient with concurrent or sequential documentation of a sebaceous neoplasm and a minimum of one internal malignancy or, multiple keratoacanthomas and a visceral malignancy and a positive family history. 3,4,18 The significance of a negative history is perhaps mitigated by reports indicating that patients with Muir-Torre syndrome typically develop their first internal malignancy at an older age.…”

Section: Discussionmentioning

confidence: 99%

MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir–Torre syndrome

2008

View full text Add to dashboard Cite

The subtype of Muir-Torre syndrome, allelic to hereditary nonpolyposis colorectal cancer is typically associated with germline mutations in the mismatch repair proteins MSH-2 and/or MLH-1. More recently, mutation in an additional mismatch repair protein MSH-6 has been documented in a patient with Muir-Torre syndrome. Given this, the aim of the present study was to ascertain the frequency of the same in unselected sebaceous gland neoplasms. Overall, we found that 59% of sebaceous neoplasms exhibited a mutation in at least one mismatch repair protein gene-a prevalence rate similar to that reported previously by others. Of interest, we found MSH-6 to be the mismatch repair protein most commonly lost 17/41 (41%), followed by MSH-2 14/41 (34%) and MLH-18/41 (20%) and the positive predictive value of each were as follows: MLH-1 88%, MSH-6 67% and MSH-2 55%. The frequency of a MSH-6 germline mutation in our cohort indicates that it is not a rare finding. Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6.

show abstract

Section: Discussionmentioning

confidence: 99%

MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir–Torre syndrome

2008

View full text Add to dashboard Cite

show abstract

“…1,2 HNPCC predisposition is caused by germline mutations in one of the known human mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6, and PMS2 (InSiGHT Mutation Database: http://www.insight-group.org/). Their inactivation may result from point mutations, identifiable in approximately 50 -80% of the HNPCC families, or from genomic rearrangements, which can be detected in up to 20% of cases.…”

Section: Introductionmentioning

confidence: 99%

Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion

et al. 2005

Self Cite

View full text Add to dashboard Cite

Colon cancers arising in most patients with hereditary nonpolyposis colorectal cancer (HNPCC) show microsatellite instability (MSI). BAT26, a quasimonomorphic polyA stretch located just 3 0 of MSH2 exon 5, is considered the most sensitive and specific marker of MSI. A total of 10 HNPCC families with large intragenic MSH2 deletions, encompassing exon 5 and intron 5, identified by multiplex ligation-dependent probe amplification (MLPA) were included in this study. The deletions under study were del1-16, del1-8, del1-7, del1-6, and del3-6, detected in 3, 1, 2, 3, and 1 families, respectively. Although all patients examined from these 10 families developed unstable tumours, 13/19 MSI-H tumours (68 %) surprisingly showed stability of BAT26. By MLPA and MSH2 sequence analyses of the BAT26-stable tumours, we demonstrated that the wild-type MSH2 allele was somatically inactivated by an identical large deletion, with complete loss of intron 5/BAT26 sequences at the tumour DNA level. We could infer that the apparent stability of BAT26 was due to the complete absence of target BAT26 sequences in the tumour sample, which results in exclusive amplification of contaminant normal DNA, containing a single copy of a wild-type stable BAT26 sequence. Identification of a subset of MSH2-related unstable tumours that are not recognized by analysis of BAT26 instability indicates that this marker should never be used alone for rapid MSI screening of HNPCC tumours. Moreover, our findings indicate that BAT26 stability in the context of MSI is strongly suggestive of the presence of a large intragenic MSH2 deletion.

show abstract

“…Adenomas usually develop in the second decade of life, with the eventual presence of hundreds to thousands of polyps (8,9). Other Turcot syndrome cases are consistent with hereditary nonpolyposis colorectal cancer and are characterized by glioblastomas or astrocytomas (10). Hereditary nonpolyposis colon cancer, like familial adenomatous polyposis, is an autosomal dominant disorder arising from mutations in one of five DNA mismatch repair genes.…”

mentioning

confidence: 99%

A Homozygous Mutation in MSH6 Causes Turcot Syndrome

Hegde

Chong

Blazo

et al. 2005

Clinical Cancer Research

View full text Add to dashboard Cite

Heterozygous mutations in one of the DNA mismatch repair genes cause hereditary nonpolyposis colorectal cancer (MIM114500). Turcot syndrome (MIM276300) has been described as the association of central nervous system malignant tumors and familial colorectal cancer and has been reported to be both a dominant and recessive disorder. Homozygous and compound heterozygous mutations in APC, MLH1, MSH2, and PMS2 genes have been reported in five families. Here we describe a nonconsanguineous Pakistani family, including a son with lymphoma and colorectal cancer diagnosed at ages 5 and 8, respectively, and an 8-year-old daughter with glioblastoma multiforme. Both children had features of neurofibromatosis type 1 including atypical cafe¤ au lait spots and axillary freckling without a family history consistent with neurofibromatosis type 1, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer. Mutational analysis was done for MLH1, MSH2, and MSH6 using denaturing highperformance liquid chromatography and sequencing of a blood sample from the daughter. A novel homozygous single base insertion mutation was identified (3634insT) resulting in a premature stop at codon 1,223 in exon 7 of the MSH6 gene. Both parents were found to be heterozygous for the 3634insT mutation. Microsatellite instability testing showed instability in the glioblastoma sample. We report here the first identification of a homozygous mutation in MSH6 in a family with childhood-onset brain tumor, lymphoma, colorectal cancer, and neurofibromatosis type 1 phenotype. Our findings support a role for MSH6 in Turcot syndrome and are consistent with an autosomal recessive mode of inheritance.

show abstract

Hereditary nonpolyposis colorectal cancer and related conditions

Cited by 73 publications

References 85 publications

MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir–Torre syndrome

MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir–Torre syndrome

Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion

A Homozygous Mutation in MSH6 Causes Turcot Syndrome

Contact Info

Product

Resources

About