RESUMEN
The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.
RESUMEN
Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.
Asunto(s)
Neoplasias de la Mama/genética , Recombinación Homóloga , Mutación , Desaminasas APOBEC/genética , Negro o Afroamericano/genética , Antígenos CD/genética , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Cadherinas/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Exoma , Femenino , Humanos , Nigeria , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteína p53 Supresora de Tumor/genética , Población Blanca/genética , Secuenciación Completa del GenomaRESUMEN
The International HapMap Consortium has developed the HapMap, a resource that describes the common patterns of human genetic variation (haplotypes). Processes of community/public consultation and individual informed consent were implemented in each locality where samples were collected to understand and attempt to address both individual and group concerns. Perceptions about the research varied, but we detected no critical opposition to the research. Incorporating community input and responding to concerns raised was challenging. However, the experience suggests that approaching genetic variation research in a spirit of openness can help investigators better appreciate the views of the communities whose samples they seek to study and help communities become more engaged in the science.
Asunto(s)
Mapeo Cromosómico , Proyecto Genoma Humano , Consentimiento Informado , Cooperación Internacional , Adulto , Niño , Femenino , Variación Genética , Genética de Población , Humanos , Masculino , PadresRESUMEN
OBJECTIVE: Previous studies suggest that the majority of breast cancer in Africans are hormone receptor negative and thus differ from breast cancer in other populations. We decided to evaluate the hormone receptor status of patients seen in our practice to see if they indeed differ from that of other populations. METHODS: We prospectively collected and analyzed tumors from consecutive patients presenting to our clinic over an 18 months period from July 2004. During the period, we saw 192 patients without previous histological diagnosis and conducted routine histological and immunohistochemical analysis of their tumors for hormone receptor status. RESULTS: Most, 65.1% of tumors were ER+, 54.7% were PR+ and 79.7% were HER2 negative. Majority of the tumors, 77.6% were luminal type A, 2.6% were luminal type B, 15.8% were basal type and the remaining 4.0% (6/152) were HER2+/ER- subtype. We found an association between hormone receptor status and tumor grade but not with stage at presentation. CONCLUSION: We conclude that there is no difference in the pattern of hormone receptors in breast cancer patients of African origin compared to other populations and urge more use of hormone manipulation for management of breast cancer in this population.