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PubMedDate not supplied

Chromosomal abnormalities in angio-immunoblastic lymphadenopathy.

Chromosomal studies have been performed in 2 patients with angio-immunoblastic lymphadenopathy. In both the cases the presence of abnormal cell lines characterized by marker chromosomes has been detected. Application of banding techniques allowed to detect the structural composition of the marker chromosome in 1 of the cases and to show a clonal evolutive pattern of the rearranged chromosomal set; In the same patient a consistent Y loss observed in the major fraction of the investigated metaphases did not appear to be related to any defined rearrangement of the karyotype. Longitudinal chromosomal studies are stressed in order to better correlate th cytogenetic abnormalities and the immunoreactive picture of the lymph nodes along the course of the disease.

Antibody Formation↗
PubMed2001

Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.

We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for P-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. Cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. Leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

CD7+ near-tetraploid acute myeloblastic leukemia M2 with double t(8;21)(q22;q22) translocations and Aml1/ETO rearrangements detected by fluorescence in situ hybridization analysis.

Near-tetraploidy is a rare cytogenetic abnormality observed in acute myeloblastic leukemia (AML). It was recently suggested that near-tetraploid AML may be associated specifically with t(8;21)(q22;q22). We report here a new case of near-tetraploid AML with double t(8;21)(q22;q22) translocations. A 61-year-old woman was admitted to our hospital because of high fever and pancytopenia. Her bone marrow was markedly hypercellular, with 72% giant and bizarre myeloblasts. These myeloblasts were positive for CD7, CD13, CD19, CD33, CD34, and HLA-DR but negative for CD2 and CD56. The patient's disease was diagnosed as the M2 subtype of AML (by French-American-British classification). Chromosome analysis revealed a karyotype of 45,X,-X, t(8;21) (q22;q22)[1]/90,XXX,-X,t(8;21)(q22;q22)x2,-9[7]/46,XX[12]. Fluorescence in situ hybridization (FISH) analysis with an AML1/ ETO probe detected 4 fusion signals on 2 der(8)t(8;21) and 2 der(21)t(8;21) in near-tetraploid cells. Reverse transcription-polymerase chain reaction analysis revealed the presence of the AML1/ETO fusion transcript. These findings suggested that near-tetraploidy may be a secondary genetic change originating from a diploid clone with t(8;21) and that 2 AML1/ETO fusion genes are generated on the der(8)t(8;21) in near-tetraploid clones. Consideration of the other reported cases suggests that the immunophenotypes of near-tetraploid AML with double t(8;21) are heterogenous, but it is possible that t(8;21)-AML with expression of CD2 or CD7 may be associated with a secondary clonal evolution to near-tetraploidy.

Antigens, CD7↗
PubMed2001

Human herpes virus 8-negative primary effusion lymphoma in a patient with a ventriculoperitoneal shunt tube.

A 60-year-old woman was referred to our hospital in 1996 due to an abdominal distension in the right lower quadrant. She had undergone a partial resection of a cholesteatoma at the right temporal lobe of the cerebrum 30 years previously, and a ventriculoperitoneal shunt (VPS) tube had been placed with drainage into the right lower peritoneal cavity. The patient developed paralytic ileus in December 1966, and ultrasound and computed tomography of the abdomen revealed a cystic mass in the right lower quadrant without lymphadenopathies or masses. Cytologic examinations of the fluid in the cystic mass revealed signs of malignant lymphoma. After the resection of the cystic mass, lymphoma cells were detected in the fluid, but the wall of the cyst consisted of only fibrous tissues. Results of immunophenotypic analysis of the lymphoma cells by immunocytochemistry or flow cytometry were positive for CD19, CD20, CD22, CD45, and HLA-DR but negative for CD45RO, CD3, CD4, and CD8. The genome of human herpes virus (HHV)-8 was not detected in the lymphoma cells, but Epstein-Barr (EB) nuclear antigen 1 and EB virus (EBV)-encoded small nuclear RNAs were detected. Chromosome analysis by the G-banding method showed complicated abnormalities including der(8)t(2;8)(q31;q24), but Southern blotting analysis suggested that the c-myc oncogene did not participate in the lymphomagenesis. The patient's disease was diagnosed as HHV-8-negative primary effusion lymphoma (PEL). The long-standing inflammatory stimulation by a VPS tube might have contributed to the clonal evolution of EBV-infected lymphocytes. resulting in the development of PEL.

Chromosomes, Human, Pair 2↗
PubMed2003

Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS).

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid disorders characterized by morphologic dysplasia in one or more cell lineages. Dysplasia in MDS is associated with insufficient production of blood cells and consecutive cytopenia(s). The natural course and prognosis of MDS vary among patients and depend on genetic defects that occur during clonal evolution. In a significant group of patients (roughly 30%) progression to secondary leukemia is observed. These patients appear to have a grave prognosis. The treatment of patients with MDS has to be adjusted to the individual situation and age in each case. In many patients, control of blast cell production by palliative cytoreduction, continuous support with red blood cells, as well as other supportive measures, seem appropriate. In other patients, however, curative therapy (chemotherapy, stem cell transplantation) should be considered. The final decision to offer curative therapy must be based on many different factors including age and the overall situation of the patient. Recently established scoring systems aimed at predicting survival and evolution of leukemia in MDS may be helpful in this regard.

Adult↗
PubMed2026

Defining and managing high-risk acute myeloid leukemia (AML) in 2026.

Acute myeloid leukemia (AML) remains a highly heterogeneous malignancy in which outcomes are particularly poor for patients classified as having high-risk disease. Traditionally, high-risk AML has been defined by adverse baseline genetic features, including complex cytogenetics, TP53 alterations, and mutations associated with secondary or therapy-related disease. However, this static, genetics-centered definition is increasingly insufficient in the modern therapeutic era. Emerging evidence supports a more dynamic and context-dependent model in which risk is shaped not only by molecular architecture but also by treatment intensity, patient fitness, measurable residual disease (MRD), and evolving resistance mechanisms. Advances in genomic profiling have refined risk stratification frameworks, including ELN 2022 for intensively treated patients and the ELN 2024 classification for those receiving less-intensive therapies. In parallel, MRD has emerged as a powerful biomarker that reclassifies patients during treatment, identifying those with persistent, therapy-resistant disease despite morphologic remission. Biologically, high-risk AML is driven by the interplay of clonal evolution, epigenetic plasticity, leukemic stem cell persistence, and protective microenvironmental and immune interactions, all of which contribute to relapse. Therapeutically, the landscape has expanded to include targeted agents, venetoclax-based combinations, and transplantation strategies, yet outcomes remain limited in key high-risk subsets, particularly TP53-mutated disease and post-venetoclax relapse. Accordingly, current strategies emphasize rational combination therapies, MRD-guided treatment adaptation, and approaches targeting both leukemic cells and their supportive niches. In 2026, high-risk AML is best understood as a dynamic, treatment-context-dependent state. Improving outcomes will require integration of precision diagnostics, biologically informed therapy, and adaptive strategies designed to anticipate and overcome resistance.

Humans↗
PubMed2001

Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage.

Aggressive mastocytosis is a form of systemic mast cell disease (SMCD) characterized by organ infiltration, bone lesions. eosinophilia and lymphadenopathies. Here we report a patient with unusual clinical features, namely osteolysis without other bone lesions commonly found in SMCD, major eosinophilia and cerebral infarction. The mast cells exhibited a classical immunophenotype (CD2+, CD9+, CD13+, CD25+, CD35+, CD45c+ and CD117+). Cytogenetic investigation showed novel complex aberrations, and clonal evolution was correlated with clinical progression. The screening for recurrent point mutations affecting the c-kit gene was negative. Mainly, the ASP816VAL substitution was not detected in our patient. Treatment with steroids and interferon was only temporarily effective.

Aged↗
PubMed1996

Transformation of severe aplastic anemia into acute myeloblastic leukemia with monosomy 7.

A cytogenetically normal man with severe aplastic anemia was treated with granulocyte colonystimulating factor (G-CSF), erythropoietin (EPO), cyclosporin A, anti-thymocyte globulin, and interleukin-6 (IL-6), which resulted in a gradual improvement in his neutrophil count and hemoglobin level. After 2 years of the therapy, monosomy 7 was detected during cytogenetic analysis of his bone marrow, which evolved during a period of 5 months into acute myeloblastic leukemia. An in vitro proliferation assay of cytokine responses showed that leukemic blasts were sensitive only to G-CSF, and not to EPO or IL-6. Although allogeneic bone marrow transplantation from an HLA-matched unrelated donor was carried out in the non-remission stage, the patient died of systemic fungal infection on day 25, without any evidence of hematological engraftment. As long-term use of cytokines and immunomo-suppressants in patients with severe aplastic anemia may induce or hasten the onset of a malignant transformation, careful attention must be paid to clonal evolution. Due to the poor prognosis of secondary myelodysplasia and leukemia, allogeneic bone marrow transplantation for such patients must be carried out early in the course of the disease.

Adult↗
PubMed2001

Evolving treatment options of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid stem cell disorders characterized by peripheral cytopenias and dysplasia of bone marrow progenitor cells. A clonal evolution can result in progressive bone marrow failure and transformation towards acute myelogenous leukemia. A patient's prognosis as estimated by the International Prognostic Scoring System, age, and co-morbidities have to be considered for the selection of various treatment options. Although supportive care remains standard therapy for low-risk MDS, a number of treatment approaches that aim to improve cytopenia in transfusion-dependent patients are currently under investigation. Among others, immunosuppressive, anticytokine, and antiangiogenic therapy will be discussed. The demethylating agents 5-azacytidine and decitabine are promising for the treatment of elderly patients with high-risk MDS. An increase of the upper age limit for allogeneic stem cell transplantation, the only curative treatment option, by the development of dose-reduced conditioning regimens may have implications for the treatment of MDS patients in the future.

Adult↗
PubMed1996

[Clonal B-cell reaction in Sjögren disease and Hashimoto autoimmune thyroiditis].

Autoimmune diseases are defined as specific, adapted immune reactions against self-antigens. These antigens were attacked by activated, autoaggressive T-Cells in most cases. However, since introduction of the MALT concept it became clear, that particularly in the autoimmune diseases of the MALT specific subpopulations of B-cells play an important role. In this study, the B-cells in the thyroid gland of 40 patients suffering from Hashimoto's disease and 25 patients with Sjögrens syndrome and enlargement of the salivary glands were immunophenotyped and molecular-genetically investigated. The molecular-genetical investigation included PCR based amplification of immunoglobulin heavy chain CDR III region and the T-cell receptor gamma chain (TCR-gamma). By immunophenotyping, in the salivary glands monocytoid B-cells could be identified as intraepithelial effector cells in nearly all cases, whereas in the thyroid gland mostly marginal zone cells in the follicle epithelium were observed. In 13 biopsy specimen from salivary gland, clonal rearrangements of TCR-gamma, and in 9 cases of patients with Sjögren's syndrome JH rearrangements could be detected. Monoclonal TCR-gamma rearrangements were identified in 9/40 patients suffering from autoimmunethyroiditis Hashimoto. In 8/40 thyroid gland biopsies a monoclonal JH-rearrangement could be found. Within 11/25 patients with Sjögren's syndrome and in 23/40 patients with M. Hashimoto polyclonal rearrangements were observed. Within all biopsy specimen of patients with monoclonal rearrangements, lymphoepithelial lesions or lymphoepithelial destructions could be identified immunohistochemically. Additionally, in 2 biopsies from salivary gland and in one specimen from thyroid gland the transition from autoimmune disease into a secondary high grade lymphoma was observed. In 26/40 patients with M. Hashimoto and in 11/25 patients with Sjögren's syndrome the transition in a subsequent low grade B cell lymphoma of MALT-type was found. These results lead to the following conclusions: 1. clonal rearrangements of tumor forming B-cells in both autoimmune diseases investigated can be interpreted as facultative malignant. 2. Intraepithelial B-cells probably are the promotors of the autoimmune process and--in case of clonal evolution and immortalisation--can be regard as causative agent in the development of primary extranodal B-cell lymphoma.

B-Lymphocytes↗
PubMed2001

[Chronic myeloproliferative disorders. The new WHO classification].

Except for chronic myelogenous leukemia (CML), chronic myeloproliferative disorders (CMPDs) include as main subtypes polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), and essential thrombocythemia (ET). A common finding in CMPDs is a clonal evolution associated with a significantly variable course, which may be complicated by thrombocythemia, (secondary) myelofibrosis, and finally acceleration (unstable phase) that merges into blastic crisis. New therapeutic modalities (chemo- and interferon therapy, bone marrow and stem cell transplantation) which were developed in the last decade and the striking differences in survival amongst the different subtypes warrant not only an unequivocal distinction from reactive and allied disorders, but a clear-cut classification as well. For this reason, a synoptical approach is essential including clinical data and, as a major diagnostic tool, a bone marrow biopsy. This concept finds expression in the new WHO classification, which also includes as rare subtypes chronic neutrophilic leukemia, eosinophilic leukemia, chronic hypereosinophilic syndrome, and finally unclassifiable entities. Histopathology of bone marrow biopsies reveals specific findings, in particular concerning megakaryopoiesis, which are characteristic for the different subtypes. These features facilitate the still controversially discussed differentiation of thrombocythemia that is frequently present, as is the case in initial (prefibrotic) IMF from ET. Moreover, in addition to clinical findings,the associated heterogeneity of bone marrow morphology indicates a stepwise evolution of the disease process and thus exerts a significant impact on survival, i.e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia.

Bone Marrow↗
PubMed2025

Integrating multi-omics approaches in acute myeloid leukemia (AML): Advancements and clinical implications.

Acute myeloid leukemia (AML) is a highly heterogeneous and aggressive hematologic malignancy characterized by clonal proliferation of myeloid precursors. Despite significant advancements in genomic profiling and targeted therapies, patient outcomes remain suboptimal due to disease complexity, resistance mechanisms, and high relapse rates. The integration of multi-omics approaches-spanning genomics, epigenomics, transcriptomics, proteomics, and metabolomics-has revolutionized AML research, offering a comprehensive understanding of leukemogenesis, tumor heterogeneity, and therapeutic vulnerabilities. Recent studies leveraging high-throughput sequencing, mass spectrometry, and advanced computational tools have uncovered novel biomarkers, clonal evolution dynamics, and microenvironmental interactions that drive AML progression and resistance. For instance, single-cell multi-omics has revealed chemotherapy-resistant leukemic stem cell populations, while proteogenomic analyses have identified actionable targets such as MCL1 and metabolic dependencies like OXPHOS. Clinically, integrated omics platforms are refining risk stratification, minimal residual disease (MRD) monitoring, and personalized therapy selection. However, challenges such as data integration complexity, cost barriers, and ethical considerations remain. This review highlights the transformative potential of multi-omics in AML, emphasizing recent advancements in technology, biomarker discovery, and therapeutic innovation. By bridging the gap between molecular insights and clinical practice, multi-omics integration promises to redefine AML management, paving the way for precision oncology and improved patient outcomes.

Humans↗
PubMed2006

Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases.

Conflicting theories of epithelial carcinogenesis disagree on the clonal composition of primary tumors and on the time at which metastases occur. In order to study the spatial distribution of disparate clonal populations within breast carcinomas and the extent of the genetic relationship between primary tumors and regional metastases, we have analyzed by comparative genomic hybridization 122 tissue samples from altogether 60 breast cancer patients, including 34 tumor samples obtained from different quadrants of 9 breast carcinomas, as well as paired primary-metastatic samples from 12 patients. The median intratumor genetic heterogeneity score (HS) was 17.4% and unsupervised hierarchical clustering analysis comparing the genetic features to those of an independent series of 41 breast carcinomas confirmed intratumor clonal divergence in a high proportion of cases. The median HS between paired primary breast tumors and lymph node metastases was 33.3%, but the number of genomic imbalances did not differ significantly. Clustering analysis confirmed extensive clonal divergence between primary carcinomas and lymph node metastases in several cases. In the independent series of 41 breast carcinomas, the number of genomic imbalances in primary tumors was significantly higher in patients presenting lymph node metastases (median = 15.5) than in the group with no evidence of disease spreading at diagnosis (median = 5.0). We conclude that primary breast carcinomas may be composed of several genetically heterogeneous and spatially separated cell populations and that paired primary breast tumors and lymph node metastases often present divergent clonal evolution, indicating that metastases may occur relatively early during breast carcinogenesis.

Alleles↗
PubMed2006

Novel analysis of clonal diversification in blood B cell and bone marrow plasma cell clones in immunoglobulin light chain amyloidosis.

Immunoglobulin light chain amyloidosis (AL) is characterized by a limited clonal expansion of plasma cells and amyloid formation. Here, we report restriction in the diversity of VL gene usage with a dominance of clonally related B cells in the peripheral blood (PB) isotype-specific repertoire of AL patients. A rigorous quantification of lineage trees reveals presence of intraclonal variations in the PB clones compared to the bone marrow (BM) clones, which suggests a common precursor that is still subject to somatic mutation. When compared to normal BM and PB B cells, AL clones showed significant but incomplete impairment of antigenic selection, which could not be detected by conventional R and S mutation analysis. Therefore, graphical analysis of B cell lineage trees and mathematical quantification of tree properties provide novel insights into the process of B cell clonal evolution in AL.

Algorithms↗
PubMed2025

Cytogenetic and molecular characterization of an atypical ETP-ALL case with BCL2 dependency: therapeutic implications for Venetoclax use.

BACKGROUND: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, high-risk subtype of T-ALL characterized by distinctive immunophenotypic and genomic features. It is often associated with induction failure and frequent relapses. Despite recent advances in its molecular characterization, the prognosis remains dismal, and effective targeted therapies are limited. METHODS AND RESULTS: We report a pediatric, multi-refractory ETP-ALL case with novel cytogenetic alterations, including a 4q deletion and a t(16;18)(q24;q21) translocation. Molecular profiling revealed progressive activation of the BCL2 pathway and disruption of Th17-related immune markers. Ex vivo sensitivity assays performed at different disease stages demonstrated increasing BCL2 dependency. Based on these findings, venetoclax was administered on a compassionate-use basis, resulting in rapid hematologic recovery and a marked reduction in blast percentage. CONCLUSIONS: This case highlights the role of clonal evolution and immune deregulation in accompanying BCL2 addiction in relapsed ETP-ALL. Altogether, our findings underscore the therapeutic potential of venetoclax in refractory pediatric ETP-ALL cases with progressive BCL2 dependency.

Humans↗
PubMed1992

Multiple myeloma and chronic lymphocytic leukemia: parallels and contrasts.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) are closely related B-cell cancers. Parallel and divergent features of these diseases are reviewed. In MM, expression of multiple hemopoietic lineage-associated antigens on the malignant cells and the substantial likelihood of progression to acute myelogenous leukemia suggest transformation of a pluripotent stem cell. In CLL, transformation more likely involves a committed B-cell progenitor. Another difference is that clonal evolution with associated cytogenetic progression is common in MM but not CLL. Other data, including studies of proto-oncogenes and tumor suppressor genes, suggest that MM results both from increased proliferation and accumulation of tumor cells, whereas tumor cell accumulation is the predominant feature of CLL. These differences may be reflected in the seemingly greater role of cytokine abnormalities in MM progression. For example, osteoclast-activating properties of some cytokines account for bone involvement in MM but not in CLL. MM and CLL share common features such as stage-dependent anemia and immune deficiency. Both diseases respond to alkylating agents but vary markedly in their sensitivity to fludarabine (CLL greater than MM) and glucocorticoids (MM greater than CLL). Differences between these diseases in progression-free interval and survival may reflect different definitions of premalignant and malignant phases rather than biologic differences. Detailed comparisons between MM and CLL may provide additional insights into these and related B-cell cancers.

Humans↗
PubMed1991

Distribution of aneuploid cell populations in ulcerative colitis with dysplasia or cancer.

Flow cytometry was used to detect the presence and assess the distribution of aneuploid cell populations in eight proctocolectomy specimens from patients with ulcerative colitis. Mucosal samples were taken according to a systematic protocol for flow cytometry, the surrounding tissue was examined histologically, and the distributions of flow cytometric and histologic abnormalities were "mapped" within each resected colon. Two resection specimens that were negative for dysplasia lacked aneuploid cell populations. Four resection specimens with final case diagnoses of dysplasia or Dukes' stage A carcinoma had 1-5 regions of aneuploidy or increased 4N (G2/tetraploid) cell populations located in discrete areas of the colon. Two specimens with dysplasia or Dukes' stage C carcinoma each had 14-15 different, often overlapping, regions of aneuploidy or increased 4N (G2/tetraploid) cell populations involving large portions of the colonic mucosa. Analysis of the DNA content of the invasive portion of the tumor from the specimen with a Dukes' stage C carcinoma showed a single aneuploid cell population. The results show that single or multiple aneuploid cell populations are often present in colons resected for ulcerative colitis with dysplasia or early cancer. The distribution of these aneuploid cell populations suggests that each represents a clone of cells that has expanded to occupy a discrete region of colonic mucosa. Additional genetic errors may result in multiple aneuploid cell populations that may be associated with an increased risk of developing cancer. These data, therefore, are consistent with the hypothesis that genomic instability and clonal evolution are associated with the progression to dysplasia and carcinoma in ulcerative colitis. Because flow cytometry can measure aneuploid cell populations in colonoscopic mucosal biopsies, it may prove to be complementary to histology for detecting patients with ulcerative colitis who are at risk for neoplastic progression.

Adult↗
PubMed1993

DNA mapping of colorectal neoplasms: a flow cytometric study of DNA abnormalities and proliferation.

BACKGROUND: There is some evidence that neoplastic development and progression evolve through a multistep process associated with hyperproliferation and genetic alterations. Therefore, changes of proliferation and of cellular DNA content within the adenoma-carcinoma sequence were studied. METHODS: Using a "mapping" procedure, 12 adenomas and 18 carcinomas were analyzed flow cytometrically and histologically. In addition, normal mucosa adjacent to and distant from the tumors was assessed in the same way. RESULTS: Of 59 adenomatous fractions, 35.6% (n = 21) were aneuploid, whereas the incidence of aneuploidy was 63.5% (54/85) in the carcinomatous sites. Additional tetraploidies were identified in 5 (8.5%) and 13 (15.3%) adenomatous and carcinomatous samples, respectively. Cell proliferation, as determined by the percentage of S-phase cells, was significantly (P < 0.001) higher in the carcinomatous specimens (14.8% +/- 0.8%; mean +/- SEM) than in the adenomatous ones (8.1% +/- 0.7%). It decreased to normal mucosa adjacent to (5.1% +/- 0.5%) and distant (5.3% +/- 0.6%) from the neoplasms. DNA mapping of the tumors revealed both distinct regions and extended areas of aneuploidy and tetraploidy. There is evidence from the mapping data that aneuploid populations arise at a single focus of the adenoma and expand over large areas before a subpopulation of cells acquires the capacity of invasion. CONCLUSIONS: These data showing consecutive DNA content abnormalities within the colorectal adenoma-carcinoma sequence provide support for genomic instability and clonal evolution as important events of tumorigenesis and progression.

Adenoma↗