Skip to main content

COVID-19 is an emerging, rapidly evolving situation.

What people with cancer should know:

Guidance for cancer researchers:

Get the latest public health information from CDC:

Get the latest research information from NIH:

Grant Details

Grant Number: 5R03CA162131-02 Interpret this number
Primary Investigator: Shen, Jie
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Mitochondrial DNA Heteroplasmy and Breast Cancer Risk
Fiscal Year: 2013


DESCRIPTION (provided by applicant): Mitochondria are crucial in many basic cellular processes. Therefore, somatic mutations in mitochondrial DNA (mtDNA) have been regarded as a hallmark of cancer. Recent advance in mtDNA research have shown that inherited genetic variations, including both single nucleotide polymorphisms (SNPs) and copy number variations, are also related to certain human cancers. However, so far, there is little known about the role of mtNDA heteroplasmies, another type of mtDNA variation, in human cancer. Heteroplasmy, which has been widely observed in mitochondrial genome, is defined as the coexistence of wild-type and variant mtDNA in the same cell and tissue. In mitochondrial related diseases, the amount of adverse variant mtDNA in a cell, called the heteroplasmy level, is an important factor in determining the amount of mitochondrial dysfunction and therefore the disease severity. In the case of human cancer, high heteroplasmy level might reflect high levels of genomic instability and mitochndrial dysfunction, and thereby increased risk of cancer. mtDNA heteroplasmy might be extremely relevant to breast cancer because oxidative stress has been suggested to play a significant role in breast cancer etiology. Considerable effort has been made to discover breast cancer susceptibility genes. However, few have been identified to date. The dilemma might be due to the fact that some of the susceptibility alleles might not reside in nuclear DNA, but in mtDNA. In my pilot study of heteroplasmy in the hypervariable (HV) regions of mtDNAs, we found the presence of length heteroplasmies in both of the HV1 and HV2 regions was associated with increased risk of breast cancer, suggesting that mtDNA heteroplasmy may be associated with breast cancer. Current research on mtDNA heteroplasmy and human diseases is significantly hindered by the lack of sensitive methods to detect mtDNA heteroplasmy. Traditional Sanger capillary sequencing not only needs significant amount of labor/time to manually inspect data but also can only detect common mtDNA heteroplasmy (more than 20-25%). Therefore, there are still large amount of mtDNA heteroplasmies are left undetected. Some of them might have significant impact on mitochondrial functions and consequently human diseases. Recent development of Next Generation Sequencing (NGS) may dramatically advance our knowledge on mtDNA heteroplasmy. NGS methods can generate vast amounts of sequencing data so it is able to detect mtDNA heteroplasmy even at low levels with high confidence. In a recent study from Vogelstein's group, using massive parallel sequencing, they detected a significant amount of novel variants and observed widespread heteroplasmy in the mtDNA of normal human cells.


Peripheral blood mitochondrial DNA copy number, length heteroplasmy and breast cancer risk: a replication study.
Authors: Shen J. , Wan J. , Song R. , Zhao H. .
Source: Carcinogenesis, 2015 Nov; 36(11), p. 1307-13.
EPub date: 2015-09-10.
PMID: 26363030
Related Citations

Effects of preanalytic variables on circulating microRNAs in whole blood.
Authors: Zhao H. , Shen J. , Hu Q. , Davis W. , Medico L. , Wang D. , Yan L. , Guo Y. , Liu B. , Qin M. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014 Dec; 23(12), p. 2643-8.
PMID: 25472672
Related Citations

Circulating miR-148b and miR-133a as biomarkers for breast cancer detection.
Authors: Shen J. , Hu Q. , Schrauder M. , Yan L. , Wang D. , Medico L. , Guo Y. , Yao S. , Zhu Q. , Liu B. , et al. .
Source: Oncotarget, 2014-07-30; 5(14), p. 5284-94.
PMID: 25051376
Related Citations

Plasma metabolomic profiles in breast cancer patients and healthy controls: by race and tumor receptor subtypes.
Authors: Shen J. , Yan L. , Liu S. , Ambrosone C.B. , Zhao H. .
Source: Translational oncology, 2013-12-01; 6(6), p. 757-65.
EPub date: 2013-12-01.
PMID: 24466379
Related Citations

Back to Top