MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps

Liang Wang, Linnea M. Baudhuin, Lisa Allyn Boardman, Kelle J. Steenblock, Gloria M Petersen, Kevin C. Halling, Amy J. French, Ruth A. Johnson, Lawrence J. Burgart, Kari Rabe, Noralane Morey Lindor, Stephen N Thibodeau

Research output: Contribution to journalArticle

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Abstract

Background & Aims:MYH-associated polyposis is a recently described disease that is characterized by multiple colorectal adenomas and a recessive pattern of inheritance. Individuals with MYH-associated polyposis have biallelic mutations in MYH, a base excision repair gene, and are negative for germline mutations in the APC gene. In this study, the 2 most prevalent MYH mutations in white persons, Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3 groups: 400 undergoing screening colonoscopy and found to have 0-3 polyps, 444 with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which a germline mutation was not identified. Methods: Genotyping for Y165C and G382D was performed by Pyrosequencing. Results: Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0-3 polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n = 26), or in those with CRC who were older than 50 years (n = 328). Furthermore, these 2 MYH mutations were not found among patients whose tumors showed the presence of defective DNA mismatch repair (n = 62). However, the presence of biallelic germline MYH mutations correlated with the presence of ≥20 adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at 50 years of age or younger also presented with biallelic germline mutations in MYH. Conclusions: These data suggest that screening of MYH should be considered not only in patients with multiple polyps but also in patients with early-onset CRC.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalGastroenterology
Volume127
Issue number1
DOIs
StatePublished - Jul 2004

Fingerprint

Polyps
Germ-Line Mutation
Colorectal Neoplasms
Mutation
Adenomatous Polyps
Colonoscopy
APC Genes
Inheritance Patterns
DNA Mismatch Repair
DNA Repair
Adenoma
Genes
Neoplasms

Keywords

  • AFAP
  • attenuated familial adenomatous polyposis
  • colorectal cancer
  • CRC
  • familial adenomatous polyposis
  • FAP
  • hereditary nonpolyposis colorectal cancer
  • HNPCC
  • mismatch repair
  • MMR
  • PCR
  • polymerase chain reaction

ASJC Scopus subject areas

  • Gastroenterology

Cite this

MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. / Wang, Liang; Baudhuin, Linnea M.; Boardman, Lisa Allyn; Steenblock, Kelle J.; Petersen, Gloria M; Halling, Kevin C.; French, Amy J.; Johnson, Ruth A.; Burgart, Lawrence J.; Rabe, Kari; Lindor, Noralane Morey; Thibodeau, Stephen N.

In: Gastroenterology, Vol. 127, No. 1, 07.2004, p. 9-16.

Research output: Contribution to journalArticle

Wang, Liang ; Baudhuin, Linnea M. ; Boardman, Lisa Allyn ; Steenblock, Kelle J. ; Petersen, Gloria M ; Halling, Kevin C. ; French, Amy J. ; Johnson, Ruth A. ; Burgart, Lawrence J. ; Rabe, Kari ; Lindor, Noralane Morey ; Thibodeau, Stephen N. / MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps. In: Gastroenterology. 2004 ; Vol. 127, No. 1. pp. 9-16.
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abstract = "Background & Aims:MYH-associated polyposis is a recently described disease that is characterized by multiple colorectal adenomas and a recessive pattern of inheritance. Individuals with MYH-associated polyposis have biallelic mutations in MYH, a base excision repair gene, and are negative for germline mutations in the APC gene. In this study, the 2 most prevalent MYH mutations in white persons, Y165C and G382D, were analyzed for their presence in 984 subjects selected from 3 groups: 400 undergoing screening colonoscopy and found to have 0-3 polyps, 444 with colorectal cancer (CRC), and 140 referred for APC mutation analysis in which a germline mutation was not identified. Methods: Genotyping for Y165C and G382D was performed by Pyrosequencing. Results: Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0-3 polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n = 26), or in those with CRC who were older than 50 years (n = 328). Furthermore, these 2 MYH mutations were not found among patients whose tumors showed the presence of defective DNA mismatch repair (n = 62). However, the presence of biallelic germline MYH mutations correlated with the presence of ≥20 adenomatous polyps. Interestingly, 2 of the 116 individuals with CRC diagnosed at 50 years of age or younger also presented with biallelic germline mutations in MYH. Conclusions: These data suggest that screening of MYH should be considered not only in patients with multiple polyps but also in patients with early-onset CRC.",
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T1 - MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps

AU - Wang, Liang

AU - Baudhuin, Linnea M.

AU - Boardman, Lisa Allyn

AU - Steenblock, Kelle J.

AU - Petersen, Gloria M

AU - Halling, Kevin C.

AU - French, Amy J.

AU - Johnson, Ruth A.

AU - Burgart, Lawrence J.

AU - Rabe, Kari

AU - Lindor, Noralane Morey

AU - Thibodeau, Stephen N

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KW - mismatch repair

KW - MMR

KW - PCR

KW - polymerase chain reaction

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