Version 1
: Received: 18 May 2021 / Approved: 20 May 2021 / Online: 20 May 2021 (12:43:11 CEST)
How to cite:
Friedenson, B. In BRCA1 and BRCA2 Breast Cancers, Chromosome Breaks Occur Near Herpes Tumor Virus Sequences. Preprints2021, 2021050490. https://doi.org/10.20944/preprints202105.0490.v1
Friedenson, B. In BRCA1 and BRCA2 Breast Cancers, Chromosome Breaks Occur Near Herpes Tumor Virus Sequences. Preprints 2021, 2021050490. https://doi.org/10.20944/preprints202105.0490.v1
Friedenson, B. In BRCA1 and BRCA2 Breast Cancers, Chromosome Breaks Occur Near Herpes Tumor Virus Sequences. Preprints2021, 2021050490. https://doi.org/10.20944/preprints202105.0490.v1
APA Style
Friedenson, B. (2021). In BRCA1 and BRCA2 Breast Cancers, Chromosome Breaks Occur Near Herpes Tumor Virus Sequences. Preprints. https://doi.org/10.20944/preprints202105.0490.v1
Chicago/Turabian Style
Friedenson, B. 2021 "In BRCA1 and BRCA2 Breast Cancers, Chromosome Breaks Occur Near Herpes Tumor Virus Sequences" Preprints. https://doi.org/10.20944/preprints202105.0490.v1
Abstract
Inherited mutations in BRCA1 and BRCA2 genes increase risks for breast, ovarian, and other cancers. Both genes encode proteins for accurately repairing chromosome breaks. If mutations inactivate this function, chromosome fragments may not be restored correctly. Resulting chromosome rearrangements can become critical breast cancer drivers. Because I had data from thousands of cancer structural alterations that matched viral infections, I wondered whether infections contribute to chromosome breaks and rearrangements in hereditary breast cancers. There are currently no interventions to prevent chromosome breaks because they are thought to be unavoidable. However, if chromosome breaks come from infections, they can be treated or prevented. I used bioinformatic analyses to test publicly available breast cancer sequence data around chromosome breaks for DNA similarity to all known viruses. Human DNA flanking breakpoints usually had the strongest matches to Epstein-Barr virus (EBV) tumor variants HKHD40 and HKNPC60. Many breakpoints were near sites that anchor EBV genomes, human EBV tumor-like sequences, EBV-associated epigenetic marks, and fragile sites. On chromosome 2, sequences near EBV genome anchor sites accounted for 90% of breakpoints (p<0.0001). On chromosome 4, 51/52 inter-chromosomal breakpoints were close to EBV-like sequences. Five EBV genome anchor sites were near breast cancer breakpoints at precisely defined, disparate gene or LINE locations. Breakpoint flanking regions resembled known EBV-cancers. Twenty-five breakpoints in breast cancers were within 1.25% of EBV cancer breakpoints. In addition to BRCA1 or BRCA2 mutations, all the breast cancers had mutated genes essential for immune responses. Because of this immune compromise, herpes viruses can activate and produce nucleases that break chromosomes. Alternatively, anchored viral episomes can obstruct break repairs, whatever the cause. The results, therefore, imply proactive treatment and prevention of herpes viral infections may prevent some chromosome breaks and benefit BRCA mutation carriers.
Keywords
Breast cancer infection; breast cancer immunity; breast cancer virus; genome biochemistry; nasopharyngeal cancer; herpes viruses; hereditary breast cancer; BRCA1; BRCA2; Burkitt's lymphoma; homologous recombination; DNA repair; viral cancer; chromosome breaks; Breast cancer infection; breast cancer immunity; breast cancer virus; nasopharyngeal cancer; hereditary breast cancer; BRCA1; BRCA2; Burkitt's lymphoma
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
