Last updated: 2025-12-18

Checks: 4 2

Knit directory: ~/Documents/TCGADataBP1Revisions/

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Seed: set.seed(12345)

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  • TGCA_BRCA
  • TGCA_OV
  • TGCA_PRAD

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For “Regulation of Antiviral and Antitumor Immunity by the BRCA1 Pseudogene in Human Cancers” we have received reviewer comment 1 as stated “1. In Figure 1, it would strengthen the study to examine BRCA1P1 expression levels specifically within BRCA1/2-mutant breast cancers-including triple-negative breast cancer-as well as ovarian and prostate tumor datasets. Additionally, incorporating solid-tumor datasets (supported by experimental evidence) that show BRCA1P1 expression patterns in cisplatin- or PARP-inhibitor-resistant models would add novelty and broaden the relevance of the findings.”

To address the reviewer’s request, we analyzed BRCA1P1 copy-number variation across multiple solid tumor types, stratified by BRCA1/2 mutation status, using publicly available TCGA Pan-Cancer Atlas datasets. This R Markdown workflow uses cBioPortal donwloads to looks at mutation annotation and copy-number segmentation data from breast (Breast Invasive Carcinoma (TCGA, PanCancer Atlas)), ovarian (Ovarian Serous Cystadenocarcinoma (TCGA, PanCancer Atlas) ), and prostate cancers (Prostate Adenocarcinoma (TCGA, PanCancer Atlas)).

For each tumor type, BRCA1 and BRCA2 mutation status was extracted and standardized at the per-sample level, allowing classification of tumors as BRCA1/2-mutant or BRCA1/2-wild-type. Copy-number segmentation data were then queried to identify the segment overlapping the BRCA1P1 genomic locus from HG19 UCSC Genome Browser (chr17:41,320,187-41,320,266).

The following Rmd will address BRCA1P1 expression patterns in cisplatin- or PARP-inhibitor-resistant models, and further stratify Breast Cancer by available TNBC status.

Breast Cancer (TCGA-BRCA) BRCA1P1 Copy Number Expression


BRCA1/2_Mut  BRCA1/2_WT 
         53         943 
# A tibble: 2 × 4
  BRCA_group      n mean_segmean median_segmean
  <fct>       <int>        <dbl>          <dbl>
1 BRCA1/2_Mut    53      -0.0844        -0.119 
2 BRCA1/2_WT    941      -0.0574        -0.0156

    Wilcoxon rank sum test with continuity correction

data:  seg.mean by BRCA_group
W = 22785, p-value = 0.2902
alternative hypothesis: true location shift is not equal to 0

Warning: The above code chunk cached its results, but it won’t be re-run if previous chunks it depends on are updated. If you need to use caching, it is highly recommended to also set knitr::opts_chunk$set(autodep = TRUE) at the top of the file (in a chunk that is not cached). Alternatively, you can customize the option dependson for each individual chunk that is cached. Using either autodep or dependson will remove this warning. See the knitr cache options for more details.

Prostate Cancer (TCGA-PRAD) BRCA1P1 Copy Number Expression


BRCA1/2_Mut  BRCA1/2_WT 
          9         480 
# A tibble: 2 × 4
  BRCA_group      n mean_segmean median_segmean
  <fct>       <int>        <dbl>          <dbl>
1 BRCA1/2_Mut     9       0.0879         0.0167
2 BRCA1/2_WT    480      -0.0223         0.0088

    Wilcoxon rank sum test with continuity correction

data:  seg.mean by BRCA_group
W = 2741.5, p-value = 0.1666
alternative hypothesis: true location shift is not equal to 0

Warning: The above code chunk cached its results, but it won’t be re-run if previous chunks it depends on are updated. If you need to use caching, it is highly recommended to also set knitr::opts_chunk$set(autodep = TRUE) at the top of the file (in a chunk that is not cached). Alternatively, you can customize the option dependson for each individual chunk that is cached. Using either autodep or dependson will remove this warning. See the knitr cache options for more details.

Ovarian Cancer (TCGA-OV) BRCA1P1 Copy Number Expression


BRCA1/2_Mut  BRCA1/2_WT 
         33         365 
# A tibble: 2 × 4
  BRCA_group      n mean_segmean median_segmean
  <fct>       <int>        <dbl>          <dbl>
1 BRCA1/2_Mut    33       -0.312         -0.475
2 BRCA1/2_WT    365       -0.346         -0.398

    Wilcoxon rank sum test with continuity correction

data:  seg.mean by BRCA_group
W = 6065.5, p-value = 0.9465
alternative hypothesis: true location shift is not equal to 0

Warning: The above code chunk cached its results, but it won’t be re-run if previous chunks it depends on are updated. If you need to use caching, it is highly recommended to also set knitr::opts_chunk$set(autodep = TRUE) at the top of the file (in a chunk that is not cached). Alternatively, you can customize the option dependson for each individual chunk that is cached. Using either autodep or dependson will remove this warning. See the knitr cache options for more details.