Abstract

Background: Global analysis of 3 human genomes of increasing levels of evolution (Neanderthal/Sapiens Build 34/Sapiens hg 38) 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 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%).

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. In particular, on 53 cases of LOH mutations analyzed for the two types of Glioblastoma and neuroblastoma cancers, the HGO optimality law is verified in 50 cases and in failure for only 3 cases, ie a percentage of validity of this universal law equal to 94.24%.

Keywords: Human genome; Cancer; Brain; Loss of heterozygosity; Biomathematics; Evolution