Role of Y chromosome in cancer

Role of Y chromosome in cancer

1. Sex differences in risk and incedence of diseases

   • 32 of 36 cancers types male preference of mortality
     • Major genetic differences: Y chromosome
       • Prone to X-linked mutations

2. Y Chromosome

   • Three regions
     • MSY
       • 23 genes and multiple pseudogenes
         • No meiotic recombination
         • Two groups
           • Group 1
             • ubiquitously
               • Balanced expresion crucial for maintain healthy conditions in men
           • Group 2
             • Specifically testis
               • Diverse functions than X homologs
       • Major Locci
         • TDF
         • GBY
           • short arm proximal to centromere
         • AZF
           • long arm
     • PAR1 and PAR2
       • 20 protein coding-genes
         • Are present in X and Y chromosome
           • Meiotic recombination
     • Heterochromatin region Yq

3. Y linked genes and cancer

   • TSPY and RMY ectopically expressed in disease
     • Normally expressed in testicular germ cells
   • Y chromosome genes influence liver cancer
   • Testis Specific Protein(TSPY)
     • Expressed in: gonocytes, spermatogonia and prophase
     • Could promote gonadoblastoma and GCTs
       • Express in some somatic cancer including liver cancer, melanoma and prostate cancer
     • Member of SE translocation assembly protein1 (SET/NAP1)
       • Histone chaperone (Shuttin and assembling)
       • Inhibitor of INHAT
         • INHAT inhibits histone acetylation
           • Suppress expresion genes
     • Overexpression: reduces G2/M phase
       • Accelerate cell proliferation
       • TSPY and TSPX same ancestor
         • Contrasting roles
     • 5 type of GCTs
       • Type-I
         • Teratoma sac tumor
       • Type-II
         • Seminomatous GCTs
       • Type-III
         • permatocytic seminoma
       • Type-IV
         • Dermoid Cyst
       • Type-V
         • hydatidiform mole

4. Overexpression of TSPX retards cell proliferation