PMC10424694_01
Hematoxylin and eosin (H&E) and immunohistochemical stainings for human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), and gross cystic disease fluid protein 15 (GCDFP-15) in samples from diagnosis, first relapse, and second relapse. All images are obtained with 200X magnification, except for HER2 and AR stainings of the second relapse (obtained with 400X and 100X magnification, respectively).
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The patient underwent a breast-wide excision with sentinel lymph node biopsy, revealing a breast carcinoma not otherwise specified (NOS), grade 2 according to Elston-Ellis classification, without expression of ER or PR, and with a HER2 score of 2+ (Figure 1) but without amplification at fluorescence in situ hybridization (FISH). PR-negative with a HER2-score of 3+ (Figure 1) but without gene amplification at chromogenic in situ hybridization (CISH). PD-L1 staining with Ventana SP142 clone was negative on tumor-infiltrating lymphocytes with an IC score of less than 1%.
Genomic analysis of the blood and tumor samples. (A) 96-mutational profile; (B) Relative contribution of the different mutational signatures identified after the decomposition of the 96-mutational profile; (C-E) Results of the copy number variations analysis for all autosomal chromosomes: blood and tumor samples using short reads data (C, D) and tumor sample using long reads data (E), respectively.
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We analyzed 16,544 SNVs for mutational changes and sequence context, and generated a plot that represents the abundance of somatic SNVs in trinucleotide contexts, which is also defined as a 96-mutational profile (see  Figure 2A ). Their relative contributions are shown in  Figure 2B . The copy number profiles for all autosomal chromosomes in the blood and tumor samples are shown in  Figures 2C, D , respectively. Nevertheless, the CNV analysis obtained with PromethION 24 (Oxford Nanopore Technologies) showed large chromosome alterations to the tumor genome ( Figure 2E ), which strongly correspond to the alteration detected using Illumina sequencing data ( Figure 2D ).