p53: The Gene that Cracked the Cancer Code
Excerpts: p53—The Gene that Cracked the Cancer Code
Luana Locke is a vivacious woman on the threshold of middle age, with a round pretty face, large hazel eyes and a tumble of wavy dark hair to her shoulders. There is such an air of robust good health about her as she sits talking over a frothy cappuccino in a busy Toronto café that if I didn’t already know something of her story I would never suspect that her life has been dogged by sickness, heartache and loss. A survivor of cancer, Luana already had long experience of the disease by the time of her own diagnosis at the age of 24. When she was just three years old, her sister Manuela, aged nine, died of a brain tumour. Of that period, Luana can only really remember being left frequently with relatives as her parents visited the hospital, her mother’s terrible grief when Manuela finally died and her own helpless desire to see her smile again.
‘I remember one time giving her a tissue and being upset because she blew her nose. I thought, “No! I gave it to you to wipe your tears.” I just remember her being really really sad.’ The little girl did not know then that her mother Giulietta was also sick. She and Luana’s father Franco, a tile-setter by trade, had emigrated from Italy to Canada a few years earlier for what they intended to be a short spell taking advantage of the high demand for skilled craftsmen. They were planning to go home to Italy—drawn partly by the fact that Luana’s Aunt Rina, her mother’s twin sister, had recently died of breast cancer at the age of 29, leaving four small children. But their plans were scuppered when their own daughter was diagnosed with a brain tumour, and then Luana’s mother began her own treatment—chemo-therapy and radiation for breast cancer.
‘She had a mastectomy, and I do have some very clear images of that time,’ says Locke. ‘I remember watching my mother as she was getting dressed, putting on her make-up, fixing her hair and slipping her prosthesis under her shirt.’ All this seemed normal, just part of life, to the small girl, until her mother’s cancer, which had responded to the initial treatment, returned and spread to her bones and killed her. Luana was six years old, and she speaks poignantly of the heartache and emptiness that filled their home, reduced now to her father, her brother David and herself, and of the fear that gripped her in bed at night that this monster might strike again and take more of her loved ones.
In fact the next person to be diagnosed was Locke herself. She was 24 years old and eight months pregnant when she noticed a tiny scab on her nipple. It would slough off from time to time leaving a small, weeping sore that would scab over again, but never seemed to heal. Keen to breast-feed her baby when it arrived and anxious therefore to clear up the spot, she eventually went to her doctor, who gave her some ointment. No one she saw as part of her routine maternity care seemed concerned, but when the spot appeared to be getting bigger despite a variety of ointments, her doctor referred her to a dermatologist, Donna McRitchie, who decided to take a biopsy.
‘Dr McRitchie said, “It will probably take about a week to get the results back, and we’ll call you,”’ says Locke, looking back across the years.
But the results came back unusually fast, and they were serious: Luana had Paget’s disease, a type of breast cancer that is often mistaken for eczema until the tumour growing secretively below the sore is advanced. Given her family history, her oncologist recommended the most radical treatment, mastectomy.
The diagnosis was a shock, but one of Luana’s first concerns was for her father. ‘Telling him was one of the hardest things I ever had to do,’ she comments quietly, looking down and stirring the froth in her coffee cup. ‘He’d already been through so much and it was just a journey I didn’t want him to have to travel again.’ In the event, Franco put on a brave face, urging his daughter and her distressed husband Paul not to look back to her mother’s and sister’s experience nearly 20 years earlier. ‘“Medical science has come such a long way since then,” he said.’
Within weeks of Luana’s diagnosis, her baby, a boy they named Lucas, was delivered by Caesarean section; her mastectomy was performed a few days later. Examination of the tissue removed at surgery revealed a highly aggressive tumour, and Luana subsequently had her other breast removed as a
precautionary measure. Her surgeons found a pre-cancerous lesion here too.
Though no one knew it until relatively recently, the root of the family’s problem is a mutation in a gene that goes by the prosaic name of p53—bestowed on it simply because it makes a protein with a molecular weight of 53 kilodaltons.
When it was discovered in 1979, the scientists involved had little idea of the huge significance of their finding: p53 has gradually revealed itself to be one of the most important players in the drama that is cancer—a master switch in our cells whose main function is to prevent tumours arising when their DNA is damaged. It has become the most studied single gene in the history of molecular biology, generating over 70,000 research papers to date and spawning a community of researchers that, notwithstanding the customary competition between scientists, is unusually collaborative. Every two years they come together from around the world for a scientific meeting, a few days of bracing, esoteric debate which adds new bits to the mighty jigsaw and fits some old ones into the existing picture.
p53 is the most commonly mutated gene in human cancer. This means that the gene is damaged and the information it carries is altered, in much the same way as a CD or computer file can be corrupted and its information scrambled. In those cases where the gene is not mutated, typically some other abnormal event in the cell is preventing it from functioning as it should. ‘There are lots of other genes you see mutant in the various tumour types,’ comments Bert Vogelstein of Johns Hopkins University in Baltimore, Maryland, ‘but p53 is one of the few that goes across the board. It’s unique in that it’s a common denominator of cancers.’
Vogelstein, who was born and brought up in the shadow of Johns Hopkins in the 1940s and went to medical school there, has been involved with p53 since its earliest days. His lab, housed today in a tall modern building of glass and light which looks out over Baltimore and down onto the warm red bricks of the old hospital, has provided some of the most important insights into the workings of the gene. ‘I think you could safely say that it’s impossible—or very difficult—to get a malignant tumour without the activity of p53 being disrupted.’
Excerpted with permission from Bloomsbury