Sporadic medulloblastomas contain PTCH mutations

Corey Raffel, Robert Brian Jenkins, Lori Frederick, Deanne Hebrink, Benjamin Alderete, Daniel W. Fults, C. David James

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Abstract

Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

Original languageEnglish (US)
Pages (from-to)842-845
Number of pages4
JournalCancer Research
Volume57
Issue number5
StatePublished - 1997

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Basal Cell Nevus Syndrome
Medulloblastoma
Loss of Heterozygosity
Mutation
Basal Cell Neoplasms
Alleles
Central Nervous System Neoplasms
Neoplasms
Basal Cell Carcinoma
Microsatellite Repeats
Genes
Exons

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Raffel, C., Jenkins, R. B., Frederick, L., Hebrink, D., Alderete, B., Fults, D. W., & David James, C. (1997). Sporadic medulloblastomas contain PTCH mutations. Cancer Research, 57(5), 842-845.

Sporadic medulloblastomas contain PTCH mutations. / Raffel, Corey; Jenkins, Robert Brian; Frederick, Lori; Hebrink, Deanne; Alderete, Benjamin; Fults, Daniel W.; David James, C.

In: Cancer Research, Vol. 57, No. 5, 1997, p. 842-845.

Research output: Contribution to journalArticle

Raffel, C, Jenkins, RB, Frederick, L, Hebrink, D, Alderete, B, Fults, DW & David James, C 1997, 'Sporadic medulloblastomas contain PTCH mutations', Cancer Research, vol. 57, no. 5, pp. 842-845.
Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Research. 1997;57(5):842-845.
Raffel, Corey ; Jenkins, Robert Brian ; Frederick, Lori ; Hebrink, Deanne ; Alderete, Benjamin ; Fults, Daniel W. ; David James, C. / Sporadic medulloblastomas contain PTCH mutations. In: Cancer Research. 1997 ; Vol. 57, No. 5. pp. 842-845.
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AU - Raffel, Corey

AU - Jenkins, Robert Brian

AU - Frederick, Lori

AU - Hebrink, Deanne

AU - Alderete, Benjamin

AU - Fults, Daniel W.

AU - David James, C.

PY - 1997

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N2 - Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

AB - Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

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