No evidence for germline PTEN mutations in families with breast and brain tumours

Abstract

Germline mutations of the PTEN gene are involved in Cowden disease, a genetic condition associated with an increased risk of breast cancer. Further somatic PTEN mutations have been found in glioblastomas and to a lesser extent in meningiomas. Therefore, PTEN germline mutations were searched for in a series of 20 unrelated women with breast cancer who also had a personal or familial breast-brain tumour history. Inclusion criteria were 1. family history of breast cancer; 2. absence of germline BRCA1 and p53 mutation; and 3. at least one case of brain tumour (glioblastoma, meningioma, or medulloblastoma) in either the index case or one of their first or second degree relatives. Any stigmata of Cowden disease was an exclusion criteria. Screening of the PTEN gene for point mutations or small rearrangements were performed using the denaturing gradient gel electrophoresis method on the 9 coding exons. No disease-associated mutation of the PTEN gene has been detected in our series. It is, thus, unlikely that PTEN is a significant BRCA predisposing locus. However, one might ask whether breast cancer cases resulting from germline PTEN mutation could occur without any mammary histological feature of Cowden disease. Int. J. Cancer (Pred. Oncol.) 84:216-219, 1999. Wiley-Liss, Inc.To date, 3 major and well-established breast cancer predisposing genes, namely BRCA1, BRCA2 and p53, have been identified. Germline BRCA1 and BRCA2 mutations are mostly associated with familial breast and/or ovarian, and with familial site-specific breast cancer history, respectively (Ford et al., 1998, for review), whereas p53 mutations predispose to Li-Fraumeni syndrome characterized by the occurrence of sarcoma, breast, adrenocortical, brain, and hematological tumours in children and young adults (Varley et al.,

Segmental overgrowth, lipomatosis, arteriovenous malformation and epidermal nevus (SOLAMEN) syndrome is related to mosaic PTEN nullizygosity

“…PTEN mutations were sought in germline and somatic DNA after PCR-based denaturating gradient gel electrophoresis (DGGE) and dye-terminator sequencing using ABI prism 377 DNA sequencer as described previously. 5 Microsatellite typing to search for 10qLOH was performed as described previously using a colorimetric-based detection (NBT -X phosphate) method for revelation. 6 Six CA repeats flanking the PTEN locus were tested.…”

Pathology of hereditary breast cancer

“…45,46 In contrast, CHEK2 and ATM are low-tomoderate-risk genes. Overall, there is little significant data relating pathology to these predisposition genes.…”

Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility

“…92 94 95 No mutations in the PTEN gene have been detected in breast cancer families and families with breast and brain cancer without features of Cowden syndrome. [96][97][98][99] In sporadic breast cancer patients, germline and somatic mutations in the PTEN gene are rare [100][101][102][103][104] even in young patients. 96 105 LOH at the PTEN locus is found in 11-41% of sporadic breast cancers, 102-104 106 but no somatic mutations have been observed in the remaining allele.…”