Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Chromosomes, Leukemias, Solid Tumors, Hereditary Cancers



I- Haematologic malignancies

II- Solid Tumours

III- Cancer-prone diseases


Haematologic malignancies


I- Myeloproliferative Syndromes (MPD)

    1. Chronic myelogenous leukaemia (CML)
    2. Polycytemia vera (PV)
    3. Idiopathic myelofibrosis
    4. Essential thrombocythemia (ET)
    5. Atypical chronic myelogenous leukemia (aCML)

II- Myelodysplastic Syndromes (MDS)

    1. Introduction
    2. Del(5q) and myeloid malignancies

III- Acute Myeloid Leukemias (AML)

    1. Introduction
    2. First group: AML with recurrent cytogenetic translocations
    3. Second group: Multilineage AML (mAML)
    4. Third group: Secondary AML
    5. Fourth group: others AML, Morpholocical and Immunophenotyping classification

IV- Acute Lymphoblastic Leukemias (ALL)

    1. Introduction
    2. t(4;11)(q21;q23)
    3. Others 11q23 (MLL)
    4. t(9;22)(q34;q11)
    5. t(12;21)(p12;q22)
    6. t(8;14)(q24;q32) and t(2;8)(p12;q24) and t(8;22)(q24;q11) variants
    7. 14q11 rearrangements
    8. B Cell/ T Cell
    9. Others
    10. Domino game

V- Non Hodgkin's Lymphomas / Chronic Lymphoproliferative Diseases

    1. B-cell chronic lymphoproliferative disorders
    2. B-cell Non Hodgkin Lymphomas
    3. T Cell



Malignant blood diseases may be classified:

Leukaemias are classified according to cytogenetics, cytology and pathology, and immunophenotype of the malignant cells. The WHO (World Health Organization) classification has replaced the FAB classification of leukaemias.



Myeloproliferations : quantitatives anomalies of the myeloid lineage.

I.1. Chronic myelogenous leukaemia (CML)

  • Malignant monoclonal process involving a pluripotent hematopoietic progenitor (therefore, most of the lineages are implicated).
  • Splenomegaly, high leukocyte count, basophilia, immature cells in the peripheral blood, low leucocyte alkaline phosphatase, bone marrow expansion with increased neutrophil lineage.
  • Prognosis: chronic phase, followed by blast crises, ending in an acute transformation; median survival was about 4 yrs before the recently introduced antityrosine kinase (imatinib mesylate) therapies.

  • Chromosome anomalies:

    Clonal evolution concept

    Other myeloproliferative syndromes:

    I.2. Polycytemia vera (PV)

    I.3. Idiopathic myelofibrosis (or agnogenic myeloid metaplasia)

    I.4. Essential thrombocythemia (ET):

    I.5. Atypical chronic myelogenous leukemia:

    Hybrid genes, with the involvement of : +/- Non Hodgkin Lymphoma in the case of FGFR1 involvement --> indicating that a stem-cell is likely to be implicated.



    II.1. Introduction

    Myelodysplasia: cells look "bizarre", dysplastic.

    II.2. Del(5q) and myeloid malignancies

    It is the most common structural rearrangement in myelodysplastic syndromes (MDS) and in acute myeloid leukemias (AML); del (5q) is accompanied with given clinical and haematological features.
    We herein summarize these three pictures as:

    RPS14 (5q33), encoding for a ribosomal protein, was recently discovered (Jan 2008) has having a major role in the 5q- syndrome.


    (or Acute Non Lymphocytic Leukaemias (ANLL))

    III.1. Introduction

    Massive proliferation of myeloid precursors; with a hiatus aspect in the maturation pyramid and entry of immature cells into the bloodstream.

    The new WHO/OMS classification replaces and completes the FAB classification (M1 to M7).



    Prognostic value of the chromosomal anomaly +++.

    III.2. First group: AML with recurrent cytogenetic translocations

    III.3. Second group: Multilineage AML

    This category is defined by the presence of multilineage dysplasia (in contrast with the t(15;17), for example, which affects only promyelocytes).

    III.4. Third group: Secondary AML


    III.5. Fourth group: others AML, classified by Morphology and Immunophenotyping of the cells



    IV.1. Introduction

    Chromosomes anomalies:

    IV.2. t(4;11)(q21;q23)

    IV.3. Other 11q23 rearrangements in leukemias

    IV.4. t(9;22)(q34;q11)

    IV.5. t(12;21)(p12;q22)

    IV.6. t(8;14)(q24;q32) and t(2;8)(p12;q24) and t(8;22)(q24;q11) variants

    IV.7. 14q11 rearrangements

    ex: t(11;14)(p13;q11), t(8;14)(q24;q11) and t(10;14)(q24;q11)

    IV.8. B Cell/ T Cell

    t(8;14)(q24;q11) MYC/TCR
    T Cell

    t(8;14)(q24;q32) / t(2;8)(p12;q24) / t(8;22)(q24;q11)
    B Cell

    IV.9. Others:

    IV.10. Domino game



    V.1. B-cell chronic lymphoproliferative disorders (CLD)

    V.2. B cell Non Hodgkin's lymphomas (NHL)

    V.3. T Cell:

    Solid Tumours (short summary)

    I- Sarcomas

    II- Carcinomas with translocations

    III- Carcinomas: colorectal cancer

    IV- Carcinomas: breast cancer/ hereditary breast cancer



    Sarcomas: it is an heterogeneous group, of many malignant tumours, often the diagnostic is hard to reach; however, a number of these tumours present a specific translocation; which can be of great help for diagnostic ascertainement.

    I-1. Lipoma: rearrangement of HMGA2 (12q15), high mobility group gene, , non histone protein, architectural factor, preferential binding to AT rich sequences in the minor groove of DNA helix.

    I-2. Liposarcoma: MDM2 amplification (NO translocation, NOR stimulation by a gene enhancer as for MYC) ; (located in 12q15, MDM2 interacts with TP53 and RB1, inhibits the cell cycle arrest in G1 phase and apoptosis); Often, neighbouring genes too, CDK4 and HMGA2, may be amplified and over-expressed.

    I-3. Inflammatory myofibroblastic tumor (see above).

    I-4. Embryonal rhabdomyosarcoma: loss of heterozygoty in 11p15 (function of IGF2, H19, CDKN1C ??); complex karyotype.

    I-5. Alveolar rhabdomyosarcoma: specific translocation t(2;13)(q35;q14); PAX3 (2q35, transcription factor implicated in proliferation, differentiation, apoptosis) and FKHR (13q14). Variant translocation: t(1;13)(p36;q14): PAX7(1p36) / FKHR.

    I-6. Ewing's tumors / Primitive neurectodermal tumours (PNET): small round-cell tumours (difficult to diagnose) deriving from neural crests cells.





    II-1. There can be specific translocations, e.g.:

    II-2. Most often, karyotypes are complex, and still poorly understandable; comparative genomic hybridization (CGH) and CGH array are particularly useful..



  • The diploid form, RER+ (Replication Error +), sporadic, without loss of heterozygoty (LOH), with few TP53 and APC, mutations, in the right-sided colon.
  • The polyploid form, RER-, with LOH 5q, 17p, 18q, p53 mutations, more often in left-sided colon, with a poorer prognosis.

    … Colorectal cancers can also be related to given cancer-prone diseases:

    III-1. Familial adenomatous polyposis (FAP): characterized by the development of hundreds of polyps at a very early age, due to mutations in APC (5q21); CTNNB1 is phosphorylated by a complex including APC, which leads to CTNNB1 degradation by the ubiquitin-proteasome; CTNNB1 is assumed to transactivate genes which may stimulate cell proliferation or inhibit apoptosis.

    III-2. Hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome: due to germline mutations in genes intervening in the repair of DNA mismatches occurring during replication (MSH2 and MLH1).




    Genes Implicated:

    … 5-10% of breast cancers are due to hereditary predisposition, with germinal mutations in:

    … Others hereditary conditions with predisposition to breast cancers:

    Cancer prone diseases

    I- Hereditary Breast Cancer, Colorectal Cancer, etc (see above)

    II- Chromosome Instability Syndromes

      1. Fanconi Anemia (FA)
      2. Ataxia telangiectasia (AT)
      3. Bloom Syndrome (BS)
      4. Xeroderma pigmentosum (XP)

    III- Retinoblastoma / Li-Fraumeni Syndrome

      1. Retinoblastoma
      2. Li-Fraumeni Syndrome and TP53

    IV- Hamarto-Neoplastic Syndromes



    Some rare genetic diseases:
      - Fanconi Anaemia (FA)
      - Ataxia Telangiectasia (AT)
      - Bloom Syndrome (BS)
      - Xeroderma pigmentosum (XP)
    are defined by:
    These diseases are defined by a high level of breaks or chromosomal rearrangements and/or a high sensibility to mutagen reagents.
    If DNA lesions are not properly repaired, mutations and genes rearrangements fast accumulate, leading to oncogene activation or antioncogene inactivation, by chance, at a time or another.

    II.1. Fanconi Anemia (FA)

    II.2. Ataxia Telangiectasia (AT)

    II.3. Bloom Syndrome (BS)

    Micro nuclei
    SCE (sister chromatid exchange)

    II.4. Xeroderma Pigmentosum (XP)



    III.1. Retinoblastoma

    Cancer prone disease at increased risk of the cancer of the retina called retinoblastoma.

    These features are unusual, and some appear contradictory...let's tell the story:

    Therefore, the gene is a recessive gene; however it seems to be transmitted with an autosomal dominant pattern in the hereditary forms; How?:

    RB1 (13q14)

    III.2. Li-Fraumeni Syndrome and TP53

  • How to suspect an hereditary cancer predisposition:
  • In 1969 FP Li and JF Fraumeni define a syndrome:

  • Mutation of various genes can lead to Li-Fraumeni Syndrome:

    ...on the other hand, somatic mutations of P53 are found in about 50% of all cancers.



  • Hamartomas are localized tissue proliferations with faulty differenciation and mixture of component tissues;
  • hamartomas are benign proliferations that have a potential towards neoplasia;
  • patients are at increased risk of benign and malignant tumors of various tissues and organs.
  • these diseases are heritable;
  • The genes known so far are tumor suppressor genes, but no common fonction has yet been established.

    … Example: NF1:

    Neurofibromatosis Type 1


    Written2000-06Jean-Loup Huret
    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
    Updated2008-02Jean-Loup Huret
    Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Wed Jul 28 18:14:59 CEST 2021

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