CNV on HSP family in human breast cancer and its relationship with gene expression

FERNANDEZ-MUÑOZ, JUAN MANUEL; CAYADO GUTIERREZ, NIUBYS DE LOS MILAGROS; FANELLI, MARIEL ANDREA; ZOPPINO, FELIPE CARLOS MARTIN

Mendoza

Congreso; Congreso Interuniversitario I+D+I Mendoza.; 2021

Universidades de Mendoza

standardized incidence rate of 47.8, and age-standardized mortality of 13.6 in 2020. BRCA can be divided according to molecular aspects in 5 subgroups (luminal A, luminal B, basal, Her2, and normal-like) with different clinical characteristics. The HSP family is composed of 95 genes subdivided into 5 subfamilies, these genes have key roles in proteostasis and they have been extensively associated with cancer behaviour. We performed CNV analysis on the TCGA breast cancer cohort. For this purpose, we used GAIA to achieve statistically significant copy number variants of genome regions. We studied the HSP family of genes, we found 25 genes amplified and 24 deleted genes. We analyzed amplifications CNVs accordingly to molecular subtypes of BC, we found a group with 5 genes (CCT3, HSPA6, HSPA7, CCT5, and ODF1) altered in all molecular subtypes. The Basal subgroup presented the mayor number of altered genes (CCT3, HSPA6, HSPA7, DNAJC5G, CCT4, CCT7, DNAJC19, DNAJB11, CCT5, DNAJC21, HSP90AB1, ODF1, HSPA14, DNAJC1, DNAJC24, DNAJC3, and HSPB6), and also presented the major number of subtype-specific amp CNVs (DNAJC5G, CCT4, CCT7, HSP90AB1, DNAJC1, DNAJC24, DNAJC3, and HSPB6). In the case of luminal tumours, Luminal A showed 12 amp CNV, with no subtype-specific alteration, and Luminal B presented 13 amp CNV, including 2 specific subtype alterations (DNAJC5B and HSPA5). Luminal A shared 4 amp CNV with Luminal B (DNAJB13, CCT2, TRAP1, and DNAJA3), 2 with Basal (DNAJB11 and HSPA14), and the alteration on DNAJC19 with Basal and Luminal B. Her2 subtypes showed a minor number of alterations (6), these include the common group to all subtypes and CNV on DNAJC21 shared with Luminal B and Basal. With respect to deletions, we found that DNAJC11, HSPB7, and DNAJC8 genes are altered across all molecular subtypes. Luminal A subtype posses the major number del CNV alterations (DNAJC11, DNAJC16, HSPB7, DNAJC8, HSPB11, DNAJC6, DNAJB4, SEC63, TCP1, DNAJC2, CRYAB, HSPB2, HYOU1, HSPA8, DNAJC15, and DNAJA2), including the altered genes DNAJC2, DNAJC15, and DNAJA2 as subtype-specific amp-CNV. Luminal B presented 15 del CNV (DNAJC11, DNAJC16, HSPB7, DNAJC8, HSPB11, DNAJC6, DNAJB4, DNAJB3, SEC63, HSPA12A, CRYAB, HSPB2, HYOU1, HSPA8, and HSPA12B), one of them as subtype-specific (HSPA12A). Luminal A shared 6 del-CNV, with Luminal B (HSPB11, DNAJC6, DNAJB4, SEC63, CRYAB, and HSPB2), altered TCP1 with Basal, and the alterations on DNAJC16, HYOU1, and HSPA8 with Basal and Luminal B. The Basal subgroup presented 15 altered genes (DNAJC11, DNAJC16, HSPB7, DNAJC8, DNAJB2, DNAJB3, HSPB3, TCP1, HYOU1, HSPA8, DNAJC22, DNAJC14, DNAJC17, CCT6B, and HSPA12B), and also presented the major number (6) of subtype-specific del CNVs (DNAJB2, HSPB3, DNAJC22, DNAJC14, DNAJC17, and CCT6B). Her2 subtypes showed a minor number of alterations (6), these include the common group to all subtypes, the specific-subtype CNV on HSPB9, also Her2 shared CNV on DNAJB3 with Luminal A and Basal, and CNV alterations in TCP1 shared with Luminal A and Basal. We observed significant differences between correlations of gene expression and CNV values of patients according to the aberration status of HSPs genes. In patients with amplifications CNVs in HSPs genes, we observed a correlation with a mean of 0.44 ±0.17. In the case of patients with deletions in HSPs, we determined a mean correlation of 0.29 ±0.11. We found a correlation mean of 0.23 ±0.1 in patients with normal values of CNV. These data suggest that CNV can affects the expression of several HSPs on BRCA.