The BRCAness Landscape of Cancer

Our plain-English summary of The BRCAness Landscape of Cancer, by M. Guo, S.M. Wang (Cells, 2022).

The study

• Authors: M. Guo, S.M. Wang
• Journal: Cells
• Published: 2022;11(23)
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

BRCAness refers to the damaged homologous recombination (HR) function due to the defects in HR-involved non-BRCA1/2 genes. BRCAness is the important marker for the use of synthetic lethal-based PARP inhibitor therapy in breast and ovarian cancer treatment. The success provides an opportunity of applying PARP inhibitor therapy to treat other cancer types with BRCAness features. However, systematic knowledge is lack for BRCAness in different cancer types beyond breast and ovarian cancer. We performed a comprehensive characterization for 40 BRCAness-related genes in 33 cancer types with over 10,000 cancer cases, including pathogenic variation, homozygotic deletion, promoter hypermethylation, gene expression, and clinical correlation of BRCAness in each cancer type. Using BRCA1/BRCA2 mutated breast and ovarian cancer as the control, we observed that BRCAness is widely present in multiple cancer types. Based on the sum of the BRCAneass features in each cancer type, we identified the following 21 cancer types as the potential targets for PARPi therapy: adrenocortical carcinoma, bladder urothelial carcinoma, brain lower grade glioma, colon adenocarcinoma, esophageal carcinoma, head and neck squamous carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, mesothelioma, rectum adenocarcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, sarcoma, skin cutaneous melanoma, stomach adenocarcinoma, uterine carcinosarcoma, and uterine corpus endometrial carcinoma.

In plain English

This study analyzed existing public genetic data. It did not study patients directly and examined no asbestos or other exposure. The authors used data from The Cancer Genome Atlas on over 10,000 cancer patients across 33 cancer types, one of which was mesothelioma. A figure gives patient numbers per cancer type, but its numbers are missing from the available text. They examined genes linked to "BRCAness", a DNA-repair fault resembling that caused by damaged BRCA1 or BRCA2 genes, using BRCA1/2-mutated breast and ovarian cancer as the reference. In BRCA1, BRCA2 and other BRCAness genes they found 808 germline (present in the body's normal cells) and 4017 somatic (arising in the tumor) harmful mutations. Gene silencing by promoter hypermethylation was common, and activity of these genes was linked with survival in many cancer types. On a combined score, 21 cancer types, mesothelioma among them, scored higher than this reference. Mesothelioma scored 23.9 against a reference total of 12.0. The authors concluded that BRCAness is common across cancers and that these 21 types are candidates for testing PARP inhibitor drugs. No treatment was tested.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: computational analysis of publicly available tumor genomic, methylation, gene expression and survival data (TCGA)
• Who was studied: Over 10,000 cancer patients in 33 cancer types from The Cancer Genome Atlas, including mesothelioma (MESO). Patient numbers per cancer type are shown in Figure 1B, but those numbers are not in the supplied text.
• Main results:
  • Across the 33 cancer types the authors identified 808 germline and 4017 somatic pathogenic mutations in BRCA1, BRCA2 and BRCAness genes
  • Prevalence of somatic pathogenic variation in BRCAness genes ranged from 0.14% to 39.81%, with TP53 highest
  • Homozygous deletion in BRCAness genes was low, at 0.01 to 1.16%, compared with 0.16% in BRCA1 and 0.32% in BRCA2
  • Using BRCA2 methylation as the cutoff, 16 of the 40 BRCAness gene promoters were hypermethylated across nearly all cancer types. Using ovarian cancer as the cutoff, 20 of the 33 cancer types had promoter hypermethylation.
  • Increased expression of the AURKA gene was correlated with worse survival in 16 of the 33 cancer types
  • 21 cancer types, including mesothelioma, had combined BRCAness feature scores higher than the BRCA1/2-mutated breast and ovarian cancer reference. In Table 1, mesothelioma's sum was 23.9 versus 12.0 for the reference, and uterine corpus endometrial carcinoma scored highest (62.1).
• The authors' conclusion: The authors concluded that BRCAness defects are commonly present in multiple cancer types and that the 21 identified cancer types are candidates for further trials to determine whether PARP inhibitor therapy is effective

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer, Ovarian cancer.

Medical terms in this study, explained in our Lexicon: Ovarian Cancer, Carcinoma, Adenocarcinoma, Lung Adenocarcinoma, Squamous Cell Carcinoma, Mesothelioma, Sarcoma.

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