Phenotype-directed analysis of genotype in early-onset, familial breast cancers.
Pathology
; 38(6): 520-7, 2006 Dec.
Article
em En
| MEDLINE
| ID: mdl-17393978
ABSTRACT
UNLABELLED Considerable heterogeneity of morphology and disease outcome exists within breast cancers (BC), which likely reflects variable molecular pathogeneses within this broad clinical group. AIM:
To evaluate the underlying genomic alterations associated with familial, early-onset BC (EOBC) phenotypes, in order to improve the management of this disease.METHODS:
Using hierarchical clustering of morphological and immunophenotypical parameters, 116 EOBC were stratified into six groups. Conventional and array-based comparative genomic hybridisation was used to analyse the genomic alterations.RESULTS:
Specific areas of genomic imbalance were associated with individual phenotypes. The largest phenotypical group was high grade, oestrogen receptor and HER-2 negative. This group contained the majority of BRCA1 germline mutation-associated tumours and commonly showed loss of chromosomal regions 5cent-5q13, 5q14-22 and 4q28-32. High mitotic rate, an important indicator of tumour cell proliferation and poor prognosis, was associated with gain of 19p, mapped within 7 Mb of the telomere. This region contains the candidate oncogene CDC34, the protein product of which is involved in ubiquitin-mediated degradation of the cyclin-dependent kinase inhibitor, p27Kip1.CONCLUSION:
Phenotype-based analysis can be used to determine the genetic changes important in subtypes of BC. Further, the different morphological phenotypes could act as a cost-effective surrogate for genotypical stratification to facilitate optimal management of this disease.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fenótipo
/
Neoplasias da Mama
/
Genótipo
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article