1. Background / Goal

Reviewer request: examine BRCA1P1 patterns in BRCA1/2-mutant vs WT tumors across TCGA solid tumor datasets (breast, ovarian, prostate), and further stratify breast cancer by basal/TNBC subtype where possible.

This notebook runs two related analyses:

Part A: RNA expression (RPKM) for BRCA + OV

Part B: CNV (seg.mean log2 ratio) for BRCA + OV + PRAD

BRCA1P1 TCGA RNA EXpression

BRCA1P1 expression was quantified using the Ensembl/HAVANA pseudogene annotation RP11-242D8.2 (ENSG00000267595), which corresponds to the BRCA1P1 locus based on identical genomic coordinates. This clone-based annotation is used in TCGA and Baylor pan-cancer pseudogene expression datasets.

## Tumor patients with expression: 837 
## Patients with mutation status: 996 
## Patients in plot table (inner join): 794 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       752
## 2 BRCA1/2 Mutant    42

## BRCA basal/TNBC N: 128

## BRCA patients with BRCA1 expression: 1064
## BRCA patients in BRCA1 plot table: 994
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       941
## 2 BRCA1/2 Mutant    53

## BRCA basal/TNBC N (BRCA1 expr): 171

## OV patients with BRCA1 expression: 201
## OV patients in BRCA1 plot table: 201
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       185
## 2 BRCA1/2 Mutant    16

## PRAD patients with BRCA1 expression: 488
## PRAD patients in BRCA1 plot table: 488
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       479
## 2 BRCA1/2 Mutant     9

## Tumor patients with expression: 412 
## Patients with mutation status: 398 
## Patients in plot table (inner join): 269 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       248
## 2 BRCA1/2 Mutant    21

## Total segments: 198581 
## Samples in CNV plot table: 994 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       941
## 2 BRCA1/2 Mutant    53
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       941      -0.0574        -0.0156      0.267
## 2 BRCA1/2 Mutant    53      -0.0844        -0.119       0.306
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 27088, p-value = 0.2902
## alternative hypothesis: true location shift is not equal to 0

## # A tibble: 2 × 5
##   subtype_group     n mean_segmean median_segmean sd_segmean
##   <fct>         <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA_Basal      171      -0.152         -0.150       0.206
## 2 Other           772      -0.0413        -0.0022      0.279
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by subtype_group
## W = 46606, p-value = 1.744e-09
## alternative hypothesis: true location shift is not equal to 0

## Total segments: 75613 
## Samples in CNV plot table: 489 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       480
## 2 BRCA1/2 Mutant     9
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       480      -0.0223         0.0088      0.146
## 2 BRCA1/2 Mutant     9       0.0879         0.0167      0.215
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 1578.5, p-value = 0.1666
## alternative hypothesis: true location shift is not equal to 0

## Total segments: 200978 
## Samples in CNV plot table: 398 
## # A tibble: 2 × 2
##   BRCA_group         n
##   <fct>          <int>
## 1 BRCA1/2 WT       365
## 2 BRCA1/2 Mutant    33
## # A tibble: 2 × 5
##   BRCA_group         n mean_segmean median_segmean sd_segmean
##   <fct>          <int>        <dbl>          <dbl>      <dbl>
## 1 BRCA1/2 WT       365       -0.346         -0.398      0.302
## 2 BRCA1/2 Mutant    33       -0.312         -0.475      0.371
## 
##  Wilcoxon rank sum test with continuity correction
## 
## data:  seg.mean by BRCA_group
## W = 5979.5, p-value = 0.9465
## alternative hypothesis: true location shift is not equal to 0