Subtypes of familial breast tumours revealed by expression and copy number profiling.

Extensive expression profiling studies have shown that sporadic breast cancer is composed of five clinically relevant molecular subtypes. However, although BRCA1-related tumours are known to be predominantly basal-like, there are few published data on other classes of familial breast tumours. We analysed a cohort of 75 BRCA1, BRCA2 and non-BRCA1/2 breast tumours by gene expression profiling and found that 74% BRCA1 tumours were basal-like, 73% of BRCA2 tumours were luminal A or B, and 52% non-BRCA1/2 tumours were luminal A.

Frequent somatic mutations of GATA3 in non-BRCA1/BRCA2 familial breast tumors, but not in BRCA1-, BRCA2- or sporadic breast tumors.

Heterozygous somatic mutations of the transcription factor, GATA-3, have recently been reported in approximately 5% breast of tumors unselected for family history. We sequenced the GATA-3 gene in 55 breast tumors from women with familial breast cancer, and found seven heterozygous somatic mutations, all in non-BRCA1/2 cases in which the frequency was 22%. In contrast, we found mutations of GATA-3 in only 4% of 81 sporadic tumors analysed.

Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors.

Approximately, 10% to 15% of serous ovarian tumors fall into the category designated as tumors of low malignant potential (LMP). Like their invasive counterparts, LMP tumors may be associated with extraovarian disease, for example, in the peritoneal cavity and regional lymph nodes. However, unlike typical invasive carcinomas, patients generally have a favorable prognosis.

Preferences for EMS transport and pediatric emergency department care.

Objectives: To characterize the reasons pediatric emergency department (PED), patients access emergency medical services (EMS) for transport to the pediatric ED. To describe the acceptability of other modes of transport and alternative sites of care.

Methods: We included a convenience sample of the responsible adults accompanying pediatric patients who arrived via EMS to the PED of an academic medical center.

BCoR-L1 variation and breast cancer.

Introduction: BRCA1 is involved in numerous essential processes in the cell, and the effects of BRCA1 dysfunction in breast cancer carcinogenesis are well described. Many of the breast cancer susceptibility genes such as BRCA2, p53, ATM, CHEK2, and BRIP1 encode proteins that interact with BRCA1. BCL6 corepressor-like 1 (BCoR-L1) is a newly described BRCA1-interacting protein that displays high homology to several proteins known to be involved in the fundamental processes of DNA damage repair and transcription regulation.

A novel corepressor, BCoR-L1, represses transcription through an interaction with CtBP.

Corepressors play a crucial role in negative gene regulation and are defective in several diseases. BCoR is a corepressor for the BCL6 repressor protein. Here we describe and functionally characterize BCoR-L1, a homolog of BCoR.

Mutation and expression analysis of LZTS1 in ovarian cancer.

LZTS1 has been shown to have tumour suppressor activities against prostate and breast cancer and is located within a region of frequent loss of heterozygosity (LOH) at 8p22 in ovarian cancer. We have analysed the expression of LZTS1 in ovarian cancer and found no evidence of loss of expression relative to normal ovarian surface epithelial cells. We have also analysed the coding region of the LZTS1 gene in 87 primary ovarian adenocarcinomas by DHPLC and detected a single silent somatic mutation.

Transfer of chromosome 8 into two breast cancer cell lines: total exclusion of three regions indicates location of putative in vitro growth suppressor genes.

Loss of heterozygosity (LOH) of the short arm of chromosome 8 occurs frequently in breast tumors. Fine mapping of the smallest regions of overlap of the deletions indicates that multiple tumor suppressor genes may be located in this region. We have performed microcell-mediated chromosome transfer of chromosome 8 into two breast cancer cell lines, 21MT-1 and T-47D.

Chromosome 8 genetic analysis and phenotypic characterization of 21 ovarian cancer cell lines.

The short arm of chromosome 8 undergoes frequent loss of heterozygosity (LOH) in ovarian adenocarcinomas. Fine mapping has identified several distinct critical regions within 8p which undergo rates of LOH of 50% or greater, suggesting that there may be more than one tumor suppressor gene located on this chromosome arm. In an effort to refine the location of these putative tumor suppressor genes by homozygosity-mapping-of-deletion analysis, we have analyzed 21 ovarian cancer cell lines with 19 polymorphic microsatellite markers from 8p.