GM02633

GM02633 LCL from B-Lymphocyte

Description:

TURCOT SYNDROME
FAMILIAL ADENOMATOUS POLYPOSIS 1; FAP1

Affected:

Yes

Sex:

Female

Age:

31 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases
Hereditary Cancers

Class

Heritable Cancer Syndromes and other Cancers

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Ethnicity

ENGLISH

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XX

Species

Homo sapiens

Common Name

Human

Remarks

Many affected members in pedigree; 46, XX; 10% of cells show random chromosome loss; 18% of cells show chromosome breaks; centromeres are fragile on chromosomes #1, #9, and #16; donor subject has a C>T change at nucleotide 643 in exon 5 of the APC gene (643C>T) resulting in the conversion of a glutamine at codon 215 to a stop codon [Gln215Ter (Q215X)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Chromosome Analysis

Gene

APC

Chromosomal Location

5q21-q22

Allelic Variant 1

611731.0022; TURCOT SYNDROME WITH MEDULLOBLASTOMA

Identified Mutation

GLN215TER; Hamilton et al. [New Eng. J. Med. 332: 839-847 (1995)] studied 14 families with Turcot syndrome and the family originally described by Turcot et al. [Dis. Colon Rectum 2: 465-468, (1959)]. Genetic abnormalities were identified in 13 of the 14 families. Germline APC mutations were detected in 10. The predominant brain tumor in these 10 families was medulloblastoma (11 of 14 patients, or 79%). In a formal risk analysis for brain tumors in familial adenomatous polyposis, Hamilton et al. (1995) found a relative risk of cerebellar medulloblastoma 92 times that found in the general population. In the other 4 of the 14 families, the type of brain tumor was glioblastoma. The glioblastomas and colorectal tumors in 3 of these 4 families and in the original family studied by Turcot et al. (1959) had replication errors characteristic of hereditary nonpolyposis colorectal cancer. In their family 2, Hamilton et al. (1995) found a truncating point mutation in APC at codon 215; a CAG-to-TAG nonsense mutation resulted in gln215-to-ter.