Identifying Genomic Alterations in Patients With Stage IV Breast Cancer Using MammaSeq: An International Collaborative Study

Abstract

Highlights-41 stage IV stage breast cancer patients of Turkish descent were sequenced using MammaSeq TM -49 single nucleotide variations and 10 copy number variations identified -PIK3CA and TP53 mutations were present in 24% and 17% of the samples respectively -37% of the samples had ERBB2/GRB7 gains and 7% had loss of BRCA2/RB1 locus -Eight clinically significant alterations were identified . CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is madeThe copyright holder for this preprint this version posted March 2, 2020. ;

Towards an integrative multi-omics workflow

“…1 ). For instance, 42 clusters in enrichment map with 35 pathways in overexpressed ERBB2 , 16 pathways in regulation of mitotic cycle , 11 pathways in moderate kinase BRAF , 10 pathways in MAPK, PI3K/Akt signaling and 8 pathways for RB1 signaling clusters are related to breast cancer or cancer biology in literature[13,14]. They are not very specific to ILC and IDC phenotypes according to our knowledge except overexpressed ERBB2 with key ERBB2 gene known to be expressed differently between ILC and IDC samples[15].…”

“…Enrichment map obtained by these Stouffer’s values consists in 20 clusters and helps to remark regulation of mitotic cycle theme with g1 transition degradation , cycle anaphase mitotic , MAPK signaling theme with diseases signal transduction and mitotic G2 phase clusters with respectively, 46, 8, 5 and 4 pathways. These biological themes are also relative to breast cancer[14] but not very specific to ILC or IDC biology. Other clusters are 3 or 2 nodes driven, among them Rho GTPases signaling could be interesting according to[18] but hiv life cycle is also present and seems to be false positive biological theme.…”

“…1 ) and only one biological cluster by enrichment map with 3 pathways. This one describes signaling nuclear receptors theme with ESR-mediated signaling pathways known to be altered in breast cancer namely with ESR gene mutation[14,15].…”

“…Among 29 biological clusters, some of them are especially correlated to ILC and IDC carcinomas literature. Indeed, Tie2 overexpressed ERBB2 (16 pathways) and AKT network PI3K (5 pathways) biological themes seen in protein features ORA, regulation signaling kit (6 pathways) and extra nuclear ESR (3 pathways) have central mutated genes and differently expressed between ILC and IDC subtypes[14,15].…”

“…The latter is directly consistent with the known biology of ILC carcinoma characterised by lack of CDH1 expression driving dysregulation of cell-cell adhesion[21] seen previously in rna features ORA as an ILC characteristic. Others clusters as kinase BRAF mutants (10 pathways) or MAPK signaling (4 pathways) detected in ORA and activated downstream FGFR3 with FGRF1, FGFR2 and FGFR3 signaling pathways could be linked to general breast cancer biology[13,14].…”