Jean-Claude Perez
Background: Global analysis of 3 human genomes of increasing levels of evolution (Neanderthal/Sapiens Build34/Sapiens hg38) reveals 2 levels of numerical constraints controlling, structuring and optimizing these genome's DNA sequences. A global constraint - called "HGO" for "Human Genome Optimum" - optimizes the genome at its global scale. The same operator applied to each of the 24 individual chromosomes reveals a hierarchical structure of these 24 chromosomes. Methods: We analyze how this HGO genomic optimum is perturbed by hundred single or multiple LOH (Loss of Heterozygosity) deletions relating to different chromosomes and cancers. Results: The generic law highlighted is stated as follows "When an LOH deletion affects a chromosome upstream of the HGO point (chromosomes 4 13). In the chromosomal spectrum, this deletion degrades the genomic optimum of the cancer genome. When an LOH deletion affects a chromosome downstream of the HGO point (chromosomes 19 22) in the chromosomal spectrum, this deletion improves the genomic optimum of the cancer genome. The exhaustive analysis of the 240 LOHs for the following 6 cases: Chromosome 13 (breast cancer), chromosome 5 (breast cancer), chromosome 10 (glioblastoma cancer), chromosome 1 (colorectal cancer), chromosome 1 (neuroblastoma cancer) and chromosome 16 (prostate cancer) obey this law in 227 cases and do not obey this law for 13 cases (success rate of our law=94.58%). In this article we will detail this type of analysis on 153 LOH relating to breast and prostate tumors affecting respectively chromosome 13, chromosome 5 (breast) and chromosome 16 (prostate). In this detailed study, the HGO law described here is verified in 143 cases out of 153 or 93.46% of favorable cases. Conclusion: The main application of this fundamental discovery will be the genomic characterization and classification of tumors, making it possible to predict the dangerousness and even the pathogenicity.
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