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Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data

Authors: Olayiwola , Ogundiran , Hardeman , Yoshimatsu , Clayton , Adeoye , AJANI Mustapha , Ademola , Khramstova G

Publication Type: Conference proceedings

Journal: 305

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Abstract

Introduction: TNBC has the highest mortality rate amongst all other breast cancer types due to its complex tumor heterogeneity and lack of well- defined molecular targets. It is known that women of African descent are two to three times more likely to develop TNBC compared to women of European ancestry, yet wide-scale genomic studies of African and African American breast tumors are limited. To elucidate genotypes and molecular subtypes associated with the most aggressive forms of breast cancer, we used the PAM50 NanoString platform to reclassify Nigerian (NG), African American (AA) and Caucasian (CA) tumors previously annotated by Immunohistochemistry (IHC), and correlated our findings to their germline genotype data obtained using high-throughput technologies.

Methods: RNAs were isolated from formalin-fixed, paraffin embedded (FFPE) tumor tissues using the High Pure Paraffin Kit (Roche) following manufacturer's protocol, and assayed on NanoString nCounter Analysis System using a custom Nano110 (PAM50 + claudin-low & VEGF signatures) probe set. Intrinsic subtyping and gene-expression data were evaluated using R statistical software. All study samples were previously annotated and subtyped by the ER/PR/HER2 IHC classifier. Genotypes were obtained from next generation sequencing or Illumina Human2.5M BeadChip platform using germline DNA from more than 2000 breast cancer cases and 2000 controls were studied.

Results: To date, Intrinsic molecular subtyping by Nano110 has been completed on 69 NG, 81 AA and 74 CA tumors. Concordance between IHC and PAM50 was 59%, which is adequate and comparable to previous studies. Basal-like subtype was overrepresented and accounted for nearly 30% of NG and AA cases, compared to 17% in CA cases. HER2-enriched subtype was overrepresented only in NG cases (9%). The proportion with Luminal A tumors were 44% NG, 56?and 68?, respectively.

Conclusions: PAM50 NanoString assay is reliable and high-throughput for molecular subtyping breast cancer using RNA extracted from FFPE tumors. Ongoing work will correlate PAM50 intrinsic subtypes to genotype data.

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Olayiwola,O. Ogundiran,T. Hardeman,A. Yoshimatsu,T. Clayton,W. Adeoye,A. AJANI,M. Ademola,A. Khramstova,G. . (0000). Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data, 76 (), 1-1.

Olayiwola,O. Ogundiran,T. Hardeman,A. Yoshimatsu,T. Clayton,W. Adeoye,A. AJANI,M. Ademola,A. Khramstova,G. . "Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data" 76, no (), (0000): 1-1.

Olayiwola,O. and Ogundiran,T. and Hardeman,A. and Yoshimatsu,T. and Clayton,W. and Adeoye,A. and AJANI,M. and Ademola,A. and Khramstova,G. and . (0000). Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data, 76 (), pp1-1.

OlayiwolaO, OgundiranT, HardemanA, YoshimatsuT, ClaytonW, AdeoyeA, AJANIM, AdemolaA, KhramstovaG, . Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data. 0000, 76 ():1-1.

Olayiwola,Oa , Ogundiran,To , Hardeman,A , Yoshimatsu,Tf , Clayton,W , Adeoye,A , AJANI,Mustapha , Ademola,A , and Khramstova,G . "Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data", 76 . (0000) : 1-1.

O.Oa O.To H.A Y.Tf C.W A.A A.Mustapha A.A & K.G , "Abstract P6-04-05: Genotype-phenotype classification of triple negative breast cancers (TNBC) in women of African descent using the PAM50 NanoString platform and genomic data" vol.76, no., pp. 1-1, 0000.

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