Why Are There No Reported Cases of Trisomy 17, the Chromosome Carrying the Tumor Suppressor Gene P53?

When the number of chromosomes in a somatic cell is one or more greater than the normal diploid number, this is called hyperdiploidy in medical biology. If only one extra chromosome is added, giving 47 chromosomes, it is called trisomy. This is a chromosomal aberration; chromosomal aberrations usually cause chromosomal diseases, and among chromosomal diseases the trisomies are the most common.

Humans have 22 pairs of autosomes and one pair of sex chromosomes. Our medical genetics textbook mentions that, among the 22 pairs of autosomes and the one pair of sex chromosomes, only chromosome 17 has no reported cases of trisomy, while all the other chromosomes do. This phenomenon is strange, and there is little literature on it; few people seem to be researching it.

Chromosome 17 carries the famous p53 tumor suppressor gene, which suppresses proto-oncogenes and prevents carcinogenesis. Many people develop cancer because the p53 tumor suppressor gene mutates and becomes inactivated, whereupon proto-oncogenes take advantage and induce carcinogenesis; chromosome 17 is therefore very closely related to cancer.

When I studied this section in our medical genetics course at school, I immediately thought of elephants. Research shows that elephants have 20-40 copies (10-20 times the human number) of the p53 tumor suppressor gene, so elephants rarely get cancer. The same nuclear radiation that causes cancer in humans and other animals does not cause it in elephants. I naturally then drew an analogy to humans: if humans had one extra chromosome 17, they would have one extra copy of the p53 tumor suppressor gene; would this not lower the probability of cancer? In theory it is possible.

For example, a chromosomal aberration called XYY syndrome is a Y-chromosome trisomy; such patients have a karyotype of 47,XYY, which compared with the normal male karyotype of 46,XY has one extra Y chromosome. Its incidence is 1 in 900 male infants. Typical features are a tall, sturdy build, normal or mildly subnormal intelligence, abnormal personality or behavior, and more pronounced male secondary sexual characteristics than average males (colloquially, more masculine). Most XYY individuals have a normal phenotype and fertility, and only a few have hypogonadism.

From these features of XYY syndrome we may speculate that, if trisomy 17 existed, such people's tumor-suppressing ability might be far more developed than that of ordinary people. After all, the p53 gene is a natural anticancer remedy produced in the course of evolution; the efficacy of man-made anticancer drugs can hardly match it.

I once guessed that perhaps chromosome 17 syndrome does not manifest clinically and therefore goes undiscovered. But a friend with a biology doctorate doing basic research at a children's hospital told me this is impossible, because newborns now all receive karyotyping; if trisomy 17 existed it would certainly be reported.

Of course, chromosome 17 carries thousands of genes, including the breast-cancer oncogene BRCA1 and the neurofibromatosis gene NF1. So if trisomy 17 did occur, it might not be a blessing. Patients might develop all kinds of signs, as in other trisomies.

However, the mutation rate of each chromosome is in principle equal; among the 22 autosomes plus 2 sex chromosomes, only chromosome 17 never shows trisomy. Behind this phenomenon there must be some biological mechanism. What mechanism, after all, causes human chromosome 17 not to show trisomy or polysomy? I could find no relevant literature on this question. Research in this area is sparse, even blank.

Medical textbooks merely mention that this phenomenon exists, without offering any explanation for it. I suspect that perhaps the p53 gene is also a double-edged sword: while suppressing cancer, it also brings many other problems, even certain fatal effects, inhibiting lifespan or reproduction.

For example, although elephants have so many copies of the p53 tumor suppressor gene, their average lifespan is only 50-70 years, shorter than that of humans, and their reproduction rate is very low. Interestingly, research shows that carriers of the breast-cancer oncogene BRCA1 have a higher reproduction rate than average. Proto-oncogenes are positively correlated with reproduction rate, while tumor suppressor genes are negatively correlated with it; for the sake of efficient reproduction, organisms may naturally select genes that favor reproductive efficiency.

I discussed this question with my course instructor. She was quite surprised, because she had not previously noticed this detail, had never thought about it, and no student had ever asked her such a question. Probably the vast majority of medical students and teachers have not paid attention to this anomaly.

She immediately queried AI on the spot. Interestingly, AI answered that trisomy 17 cases do exist, and even stated that trisomy 17 syndrome causes leukemia. The only explanation for this result is that AI made an error and fabricated a nonexistent medical phenomenon.

AI merely exercises its reasoning ability, logically deducing that trisomy 17 cases should exist, but cannot judge whether its own reasoning is correct. Medical textbooks are rigorous; they do not lightly assert the existence of a phenomenon merely through logical deduction. In the life sciences there are too many unanswered questions to draw conclusions by logic alone. This is also a shortcoming of AI, and it affects AI's credibility.

I discussed this question on WeChat with a biology postdoc who graduated from Zhejiang University and who is currently doing tumor-related research; he too became interested. But after searching, he only found a 1962 report mentioning that five chromosomes (where there should be four) were found on chromosomes 17 and 18 in a certain patient.

This report cannot serve as evidence that trisomy 17 exists, because the extra chromosome was very likely an additional chromosome 18. Trisomy 18 is also called Edwards syndrome, with an incidence of 1 in 8,000 to 1 in 3,500 newborns—not rare. Beyond this, there are almost no reports related to trisomy 17, though there are reports related to chromosome 17 mosaicism. However, mosaicism and trisomy are after all two different things and cannot be conflated.

My biology doctorate friend guessed whether the p53 gene itself automatically causes apoptosis of this kind of aberration on chromosome 17. After all, the greatest function of the p53 gene is to induce apoptosis of problematic cells. But no related research yet supports this conjecture. I hope biologists will take up this topic in the future; such research might help us solve some cancer-related problems.

This friend also suggested designing an experiment: knock out the p53 locus, then induce with colchicine, and see the probability of chromosome 17 aberration to determine whether this is the cause. But such an experiment is not easy to carry out. For now I merely record this immediate thought and discussion, to find an answer in the future.