Single nucleotide polymorphism patterns associated with a cancer resistant phenotype

June K Dunnick; Arun R Pandiri; Keith R Shockley; Ronald Herbert; Deepak Mav; Dhiral Phadke; Ruchir R Shah; B Alex Merrick

doi:10.1016/j.yexmp.2022.104812

Single nucleotide polymorphism patterns associated with a cancer resistant phenotype

Exp Mol Pathol. 2022 Oct:128:104812. doi: 10.1016/j.yexmp.2022.104812. Epub 2022 Jul 21.

Authors

June K Dunnick¹, Arun R Pandiri², Keith R Shockley³, Ronald Herbert², Deepak Mav⁴, Dhiral Phadke⁴, Ruchir R Shah⁴, B Alex Merrick⁵

Affiliations

¹ Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. Electronic address: dunnickj@niehs.nih.gov.
² Comparative and Molecular Pathogenesis Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
³ Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
⁴ Sciome, LLC, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
⁵ Mechanistic Toxicology Branch, National Institute of Environmental Health Sciences, Division of the National Toxicology Program, Research Triangle Park, NC 27709, USA.

Abstract

Background and aims: In this study ten mouse strains representing ~90% of genetic diversity in laboratory mice (B6C3F1/J, C57BL/6J, C3H/HeJ, A/J, NOD.B1oSnH2/J, NZO/HILtJ, 129S1/SvImJ, WSB/EiJ, PWK/PhJ, CAST/EiJ) were examined to identify the mouse strain with the lowest incidence of cancer. The unique single polymorphisms (SNPs) associated with this low cancer incidence are reported.

Methods: Evaluations of cancer incidence in the 10 mouse strains were based on gross and microscopic diagnosis of tumors. Single nucleotide polymorphisms (SNPs) in the coding regions of the genome were derived from the respective mouse strains located in the Sanger mouse sequencing database and the B6C3F1/N genome from the National Toxicology Program (NTP).

Results: The WSB strain had an overall lower incidence of both benign and malignant tumors compared to the other mouse strains. At 2 years, the incidence of total malignant tumors (Poly-3 incidence rate) ranged from 2% (WSB) to 92% (C3H) in males, and 14% (WSB) to 93% (NZO) in females, and the total incidence of benign and malignant tumor incidence ranged from 13% (WSB) to 99% (C3H) in males and 25% (WSB) to 96% (NOD) in females. Single nucleotide polymorphism (SNP) patterns were examined in the following strains: B6C3F1/N, C57BL/6J, C3H/HeJ, 129S1/SvImJ, A/J, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. We identified 7519 SNPs (involving 5751 Ensembl transcripts of 3453 Ensembl Genes) that resulted in a unique amino acid change in the coding region of the WSB strain.

Conclusions: The inherited genetic patterns in the WSB cancer-resistant mouse strain occurred in genes involved in multiple cell functions including mitochondria, metabolic, immune, and membrane-related cell functions. The unique SNP patterns in a cancer resistant mouse strain provides insights for understanding and developing strategies for cancer prevention.

Keywords: Cancer; Immune; Membrane-related functions; Metabolic; Mitochondria; Mouse strains; Single nucleotide polymorphisms.

Publication types

Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural

MeSH terms

Amino Acids / genetics
Animals
Female
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, Inbred Strains
Neoplasms* / genetics
Phenotype
Polymorphism, Single Nucleotide* / genetics

Substances

Amino Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding