Cancer Cytogenetics PDF

Cancer Cytogenetics Prepared by: Cherries V. Sanchez, RMT, MSMT Department of Medical Technology College of Health Sciences National University - Manila  Cancer Multiple and sequential genetic mutations...

Cancer Cytogenetics Prepared by: Cherries V. Sanchez, RMT, MSMT Department of Medical Technology College of Health Sciences National University - Manila  Cancer Multiple and sequential genetic mutations occurring in a somatic cell. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Leukemia Uncontrolled proliferation of one or more of the various hematopoietic cells. Associated with many changes in the circulating cells of the blood. 2 main classifications of leukemia Lymphocytic ALL → Acute Lymphoblastic Leukemia CLL → Chronic Lymphocytic Leukemia Myelocytic AML → Acute Myeloid Leukemia CML → Chronic Myelogenous Leukemia No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Acute VS Chronic ACUTE CHRONIC Children & young adults Middle age and elderly Sudden onset Insidious onset weeks to months years Blast cells Mature cells AML = myeloblast CML=granulocytes ALL= lymphoblast CLL=lymphocytes No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Acute Myeloid Leukemias (AML) Classification - FAB No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Acute Myeloid Leukemias M0: Minimally differentiated M1: Myeloblastic leukemia without maturation M2: Myeloblastic leukemia with maturation M3: Hypergranular promyelocytic leukemia M4: Myelomonocytic leukemia M4Eo: variant, increase in marrow eosinophils M5: Monocytic leukemia M6: Erythroleukemia M7: Megakaryoblastic leukemia No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Acute Lymphoblastic Leukemia L1 → ALL, child L2 → ALL, adult L3 → ALL, (Burkitt) No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. L1 Acute Lymphoblastic Leukemia ALL-pre B t(1;19) No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. L2 Acute Lymphoblastic Leukemia ALL-T t(11;14) No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. L3 ALL-Burkitt’s lymphoma t(2;8), t(8;14), t(8;22) No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Chronic Myelogenous Leukemia First malignancy to be associated with a specific chromosome defect. 95% of patients → Philadelphia chromosome translocation t(9;22)(q34;q11.2) ABL1 gene→ Abelson murine leukemia viral oncogene homolog 1 (Chromosome 9) BCR gene → Breakpoint cluster region (Chromosome 22) Activates tyrosine kinase→ signal to drive proliferation of the cell No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Chronic Myelogenous Leukemia Philadelphia Chromosome t(9;22) Proliferation of mature granulocytes Found mainly in adults 45 years of age and older Blood findings include mild anemia an WBC markedly increased, may have a few circulating blasts No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Chronic Lymphocytic Leukemia (CLL) Trisomy of chromosome 12 t(14;18)(q32;q21) No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Myelodysplastic Syndrome Acquired clonal disorder affecting stem cells. Stem cell disorder with ineffective hematopoiesis Defects in maturation of all cell lines of myeloid lineage. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Of all MDS cases, 30% to 40% end in an AML NORMAL MDS Blast < 20% AML Blast > 20% No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. MDS Characteristic karyotype anomalies involve mainly chromosomes 5, 7, and 8 The most frequent abnormalities: del 5q Monosomy 7 Trisomy 8 Unbalanced translocations are relatively frequent. For example: Unbalanced t(5; 17) and t(7; 17) Translocations lead to 17p deletion No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Molecular Alterations MDS Genetic Defects The most common mutations : Chromosome 17 p arm TP53 gene (Tumor protein 53) → Regulates the cell cycle Chromosome 21 q arm RUNX1 gene (Runt related transcription factor 1) → Control the development of blood cells Chromosome 4 q arm TET2 gene (Tet methylcytosine dioxygenase 2 ) → Regulating the process of transcription No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Solid Tumors Breast cancer Prostate cancer No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Breast Cancer No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Breast Cancer HER2 BRCA1 BRCA2 PALB2 No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. HER2 / ERBB2 Human epidermal growth factor receptor 2 Erythroblastic oncogene B 2 Chromosome 17 q arm HER2 genes→ HER2 proteins (HER2/neu proteins) HER2 proteins are receptors on breast cells Controls the growth, division and repair of breast cells Mutation→ HER2 gene amplification No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  HER2 No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. BRCA genes Breast cancer gene Human tumor suppressor gene BRCA 1 → Chromosome 17 BRCA 2→ Chromosome 13 No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. PALB2 gene Partner and Localizer of Breast Cancer 2 (BRCA2) Chromosome 16 p arm DNA damage repair No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Prostate Cancer No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. Prostate Cancer Chromosomal Deletion: 5q, 6q, 8p, 10q, 13q, 16q, 17p, and 18q Chromosomal Insertion: 7p/q, 8q, 9p, and Xq Chromosomal rearrangement in 21q No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.  Target genes for 2 common Chromosomal Aberrations in Prostate Cancer AR gene (androgen receptor) at Xq12 TMPRSS2 and ERG fusion at 21q Transmembrane protease serine 2 Erythroblast transformation specific-Regulated Gene→ Transcriptional regulator No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. AR gene (androgen receptor) at Xq12 No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law. TMPRSS2 and ERG fusion at 21q No part of this material may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the owner, except for personal academic use and certain other noncommercial uses permitted by copyright law.