In 1998 and in 2000, researchers at Johns Hopkins University reported that colorectal cancer cell lines and primary tumors from the bladder, head, neck, and lung harbor mutations, deletions, and insertions in the 16.6-kilobase mitochondrial genome. Add prostate and breast cancers to that list, according to posters at the AACR meeting presented by groups from Emory University and Johns Hopkins. At one poster, John A. Petros, an associate professor of urology at Emory, described a study that he says shows for the first time that mitrochondrial DNA [mtDNA] mutations can enhance tumor growth. After he and colleagues, including Emory's Douglas C. Wallace, introduced such a mutation into a prostate cancer cell line, the cells proliferated 50 percent faster and underwent apoptosis four times less than nonmutant cells. Sixty days after the group implanted the cells into mice, tumors derived from cells containing mutant mtDNA were 10 times larger than tumors from wild-type cells. "I don't think that, by themselves, [mtDNA mutations] would be sufficient to cause cancer," remarks Petros. His hypothesis: The mutation interferes with oxidative phosphorylation. This leads to the creation of more reactive oxygen species such as hydrogen peroxide, which then signal tumors to grow. An alternative hypothesis that is posited, especially about noncoding mtDNA mutations, is that they exist in a cell before it turns malignant. During clonal expansion, mutant--rather than wild-type--mtDNA stochastically becomes concentrated in tumor cells. At another poster, Paola Parrella, a postdoc with Hopkins' David Sidransky, says she believes that clinicians might eventually use fine-needle aspiration to withdraw mtDNA in order to detect breast cancer.
Down's Syndrome Linked to Cancers
Remember Corky Thatcher, the teenage son with Down's syndrome (DS) on the 1990s TV series Life Goes On? In recent decades, people with DS have moved more into the mainstream. But their extra chromosome 21 creates health problems that are harder to eradicate than social isolation. A study of the hospitalization records of 4,872 people with DS in Denmark and Sweden, for example, shows higher risks of several cancer types. Presented at the AACR meeting by National Cancer Institute fellow Deirdre A. Hill, the study found a 26-fold excess of acute leukemias, a result consistent with previous population studies. Researchers also discovered that males with DS have a threefold excess of testicular cancer, a finding suggested by earlier case histories. The study broke new ground, however, in uncovering a slightly increased risk of digestive system cancers and a sharply higher risk of liver cancer in people with DS. It found only 11 cases of these cancers, but the excess over cases in the non-DS population was statistically significant. Noting that people with DS are more susceptible to various infectious diseases, Martha S. Linet, a senior investigator at NCI who helped conduct the study, says that their risks of developing certain cancers "could be related to their decreased immune competence." Alternatively, some of the 225 genes on chromosome 21 might contribute to these cancers. What's now needed, Linet concludes, are mechanistic studies that examine interactions between those genes, the immune system, and the environment.
