Sick as a dog

Shirley LaFlamme's bullmastiff, Halo, died last year of cancer. Two of her other dogs are fighting cancer now. She hopes her fourth will avoid the same fate.

''Cancer is absolutely what is killing most of the dogs in our breed," said LaFlamme, of Spencer.

Their battle could help provide vital clues to fighting tumors in people. It turns out that cancers and other dog diseases are similar to those in humans, and researchers at Cambridge's Broad Institute and elsewhere are delving into the genetic code of dogs hoping to find cures for both species.

Last year, the Broad scientists were the first to sequence the complete dog genome. This year, they have been touring dog shows and posting notices on Internet sites, soliciting blood samples from purebred dogs like LaFlamme's to try to map the genetic differences between healthy and sick dogs. They are addressing bone cancer common to both species, as well as tumors that arise in blood vessels, breast tissue, and skin.

''There are so many . . . dog diseases that really resemble human diseases, and the genes that are responsible for them are probably the same in dogs and humans," said Dr. Ewen Kirkness, investigator at The Institute for Genomic Research in Maryland, another nonprofit research institute that is involved in analyzing dog and human genomes.

A few years ago, a research team at Stanford University proved the point when they found that many people with narcolepsy are missing the same protein that is absent in Doberman pinschers with the sleeping disorder. That discovery led to a new understanding of narcolepsy and is being used to develop therapies for patients of both species.

Dogs provide researchers several distinct advantages for understanding human diseases: Their genes are similar to humans', and in addition to cancers and narcolepsy, specific breeds of dogs are plagued with a number of genetic maladies that also affect people. (People cannot catch them from their pets). Dachshunds can develop epilepsy, chow chows get bald spots, and bull terriers chase their tails obsessive-compulsively.

Mice and rats are the more commonplace subjects for laboratory studies, but researchers often have to trick rodents into developing tumors they wouldn't get naturally, by tampering with their genome, injecting the animals with tumor cells, or showering them with chemicals. Such cancers may not reflect what is going on in the body of a person who has lived a healthy life for decades before a diagnosis of cancer.

''Dogs live with humans, so they share our environment and they get spontaneous cancers the way that humans do," said Kristin Lindblad-Toh, codirector of the Genome Sequencing and Analysis Program at the Broad Institute, a two-year-old research group formed jointly by Harvard University and the Massachusetts Institute of Technology.

Studying genetics in dogs is also easier than in humans, in part because the record-keeping for purebreds is better than for people. Records of specific pedigrees are often kept for generations, along with the diseases each animal suffered.

In addition, because of inbreeding, purebred animals are very similar to each other genetically -- which makes it easier for researchers to spot genes that are different between the healthy and sick animals. Inbreeding also likely explains why certain diseases are more common in particular types of dogs. Any disease genes present in a dog's ancestors will be more common in that animal's descendants.

This phenomenon occurs in geographically or socially isolated human populations, too, and scientists have long taken advantage of that fact to track down disease genes, finding a gene linked to Huntington's disease, for example, by researching native tribes in Venezuela.

At the Broad Institute, Lindblad-Toh's primary target is finding the genes that cause osteosarcoma, one of the most common types of bone cancer in both canines and people. By analyzing hundreds of samples of dog blood, the researchers hope to narrow down the location of candidate genes within the genome. Differences between healthy dogs and those with cancer can be as small as a single DNA base out of billions of pairs.

Osteosarcoma, which usually grows in the long bones of the leg, but often spreads before it is caught, occurs most often in the males of both species.

In dogs, the disease is more frequently seen in larger breeds such as rottweilers, greyhounds, and golden retrievers; Several recent studies have shown that osteosarcoma is also more common in taller people, although the reason for this association is not known.

''Dogs are a beautiful model for the human disease," said Lisa Barber, professor of clinical science at the Tufts School of Veterinary Medicine, who collaborates with the Broad researchers.

Finding the genes responsible for osteosarcoma may help in the development of new screening strategies, so that carriers can be identified and patients can be diagnosed at an earlier stage, when surgery, chemotherapy, and radiation -- used to treat both human and pet patients -- are more effective.

Knowing what genes are responsible for this disease will also help scientists devise new strategies for treating it.

Dog owners like LaFlamme have played a critical role in supporting this cancer research. After Halo died, LaFlamme began organizing dog competitions; the first one raised $48,000 for canine health research and collected 300 blood samples for scientists at the Broad.

Dogs and their owners have been very receptive to the research effort, often lining up at dog shows to participate in the studies.

''Sometimes you are given a diagnosis, and you think there is nothing you can do, but even having your dog's blood sample sent in is a way you can make a difference," said LaFlamme.

To contribute a blood sample from a purebred dog for this research, please visit the Broad Institute's website www.broad.mit.edu/mammals/dog/vet_samples.html.