Gene expression profiling of breast cell lines identifies potential new basal markers.

A better molecular characterization of breast cell lines (BCL) may help discover new markers to apply to tumour samples. We performed gene and protein expression profiling of 31 BCL using whole-genome DNA microarrays and immunohistochemistry (IHC) on 'cell microarrays' (CMA), respectively. Global hierarchical clustering discriminated two groups of BCL: group I corresponded to luminal cell lines, group II to basal and mesenchymal cell lines.

How to best classify breast cancer: conventional and novel classifications (review).

Breast cancer is a complex disease and different classifications, mostly based on clinical and pathological features, have been used for guiding the management of patients. Most of them fail to reflect breast cancer heterogeneity, which could be the reason why the treatment fails in approximately 30% of cases. Emerging molecular studies based on gene expression profiling using DNA microarrays have defined new molecular subtypes of breast cancer associated with the cell-of-origin distinction.

Typical medullary breast carcinomas have a basal/myoepithelial phenotype.

Medullary breast cancer (MBC) is a rare, diagnostically difficult, pathological subtype. Despite being high grade, it has a good prognosis. MBC patients have an excess of BRCA1 germ-line mutation and reliable identification of MBC could help to identify patients at risk of carrying germline BRCA1 mutations or in whom chemotherapy could be avoided.

Myeloproliferative disorders: the centrosome connection.

Some myeloproliferative disorders (MPD) result from a reciprocal translocation that involves the FGFR1 gene and a partner gene. The event creates a chimeric gene that encodes a fusion protein with constitutive FGFR1 tyrosine kinase activity. FGFR1-MPD is a rare disease, but its study may provide interesting clues on different processes such as cell signalling, oncogenesis and stem cell renewal.

Oncogenic tyrosine kinase of malignant hemopathy targets the centrosome.

Myeloproliferative disorders (MPD) are malignant diseases of hematopoietic progenitor cells. Many MPDs result from a chromosomal translocation that creates a fusion gene encoding a chimeric kinase. The fibroblast growth factor receptor 1 (FGFR1)-MPD is characterized by the fusion of the FGFR1 kinase with various partners, including FOP.

An evolutionary history of the FGF superfamily.

Fibroblast growth factors (FGF) are associated with multiple developmental and metabolic processes in triploblasts, and perhaps also in diploblasts. The evolution of the FGF superfamily has accompanied the major morphological and functional innovations of metazoan species. The study of FGFs throughout species shows that the FGF superfamily can be subdivided in eight families in present-day organisms and has evolved through phases of gene duplications and gene losses.

ETV6 gene rearrangements in invasive breast carcinoma.

The ETV6/TEL gene encodes a transcription factor frequently rearranged in several types of cancer. We looked for ETV6 rearrangements in invasive breast cancer using fluorescence in situ hybridization (FISH) of BAC probes on sections of tissue microarrays containing 632 tumor samples. Of these samples, signal of sufficient quality for screening by FISH was obtained for 356.

Dual lympho-myeloproliferative disorder in a patient with t(8;22) with BCR-FGFR1 gene fusion.

The case of a patient presenting with a myeloproliferative disorder (MPD) characterized by a t(8;22) (p12;q11) translocation was investigated. The rearrangement resulted in the production of BCR-FGFR1 and FGFR1-BCR chimeric transcripts after in-frame fusions of BCR exon 4 with FGFR1 exon 9 and FGFR1 exon 8 with BCR exon 5, respectively. The four previously reported patients with such translocation presented with an atypical chronic myeloid leukemia (CML) without Philadelphia chromosome.

Junctional recruitment of mammalian Scribble relies on E-cadherin engagement.

Members of the LAP protein family, LET-413 in Caenorhabditis elegans, Scribble in Drosophila melanogaster, and Erbin, Lano, Densin-180 and hScrib in mammals, have conserved structural features. LET-413 and Scribble are junctional proteins involved in establishing and maintaining epithelial cell polarity. scribble also behaves as a neoplastic tumor suppressor gene.

Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling.

Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n = 36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays.

Inoperable recurrence after breast-conserving surgical treatment and radiotherapy.

Factors associated with inoperable local recurrence were investigated by a clinical and pathologic review of 596 patients with Stages I and II carcinoma of the breast treated by breast-conserving operations and megavoltage radiotherapy. After a median follow-up period of 71 months, 13 of 70 local recurrences observed were anatomically unsuitable for salvage surgical treatment, affecting 2.2 per cent of patients initially treated.

An assessment of extensive intraductal component as a risk factor for local recurrence after breast-conserving therapy.

The influence of extensive intraductal component (EIC) on local recurrence risk was studied for 496 patients with stage I-II infiltrating ductal cancers treated by conservative surgery and irradiation. EIC was diagnosed in 65 of 231 (28%) premenopausal and 41 of 265 (15.5%) post-menopausal patients.

Why are local recurrences after breast-conserving therapy more frequent in younger patients?

The influence of patient age on risk of recurrence in the breast was retrospectively studied in 496 stage I-II invasive ductal carcinomas treated by macroscopically complete primary tumor excision followed by radiotherapy. With a median follow-up of 71 months, local recurrence occurred in 13 of 62 (21%) patients younger than 40 years, compared with 48 of 434 (11%) older patients (P less than .025).