Term
| What is the definition of neoplasia? |
|
Definition
| "New growth" - an unregulated monoclonal proliferation of genetically altered ells |
|
|
Term
| What is the difference between a benign and a malignant neoplasm? |
|
Definition
| Benign = tumor remains localized, malignant = cancer that can invade and metastasize |
|
|
Term
| What are the malignant tumors that end with the suffix "oma"? |
|
Definition
| Lymphoma, melanoma, mesothelioma, seminoma |
|
|
Term
| What are important histopathological features of benign tumors? |
|
Definition
| Well differentiated, absent to mild pleomorphism (variation in size/shape of cells/nuclei), close to normal nuclear morphology, few or no mitoses, polarity, no tumor giant cells |
|
|
Term
| What are important histopathological features of malignant tumors? |
|
Definition
| Some loss of differentitation, pleomorphism (variation in size/shape of cells/nuclei), nuclear enlargement, hyperchromasia, large nucleoli, numerous atypical mitoses, loss of polarity, tumor giant cells present |
|
|
Term
|
Definition
| The replacement of one type of cell with another type |
|
|
Term
| Metaplasia is nearly always found in association with what action? |
|
Definition
|
|
Term
|
Definition
| "Disordered growth" - principally occurs in epithelium, characterized by cells with some anaplastic features and loss of polarity, may or may not progress to cancer |
|
|
Term
| What is carcinoma in situ? |
|
Definition
| Occurs when dysplastic changes involve the full thickness of the epithelium, considered "pre-invasive cancer" that will eventually progress to an invasive carcinoma |
|
|
Term
| What factors determine the rate of tumor growth? |
|
Definition
| Doubling time of the tumor cells, fraction of tumor cells in the proliferative pool (growth fraction), rate at which cells are shed or die |
|
|
Term
| How is tumor growth associated with a shortening of cell cycle time? |
|
Definition
|
|
Term
| The rate at which tumors grow is primarily determined by what? |
|
Definition
| An excess of cell production over cell loss |
|
|
Term
| ChemoRx is usually prescribed to what type of tumors? |
|
Definition
| Tumors with high growth fractions |
|
|
Term
| What are some unique gross features of benign tumors? |
|
Definition
| Nearly always grow as well circumscribed masses that are localized, often have fibrous capsule, non invasive, freely movable and readily surgically excised |
|
|
Term
| What are some unique gross features of malignant tumors? |
|
Definition
| Invasive, poorly circumscribed and fixed to surrounding tissue, surgical resection difficult or impossible |
|
|
Term
|
Definition
| Tumor implants discontinuous with the primary tumor, unequivocally marks tumor as malignant |
|
|
Term
| How does seeding of body cavities and surfaces occur in metastatic spread? |
|
Definition
| Occurs when a tumor penetrates into a body cavity, particularly characteristic of ovarian carcinomas |
|
|
Term
| How do lymphatics serve as a mechanism for metastatic spread of cancer? |
|
Definition
| Most common pathway for initial spread of carcinomas, follows natural routes of lymphatic drainage |
|
|
Term
| What is a "sentinel lymph node"? |
|
Definition
| The first node in a regional lymphatic chain that receives lymph flow from the primary tumor |
|
|
Term
| How does cancer spread through hematogenous means? |
|
Definition
| Most typical with sarcomas, occurs due to tumor penetrating into veins, liver and lungs are most frequent sites involved, can also spread intot he vertebral column |
|
|
Term
| What are the three categories of genetic predisposition to cancer? |
|
Definition
| Autosomal dominant inherited cancer syndromes, defective DNA-repair syndromes, familial cancer |
|
|
Term
| What are the characteristics of autosomal dominant inherited cancer syndromes? |
|
Definition
| Inheritance of single mutant gene greatly increases risk of cancer, usually a point mutation, tumors within this group are often associated with a specific marker phenotype |
|
|
Term
| What are some examples of common autosomal dominant inherited cancer syndromes? |
|
Definition
| Retinoblastoma, familial adenomatous polypsosis |
|
|
Term
| What are the characteristics of defective DNA-repair syndromes? |
|
Definition
| Group of cancer-predisposing conditions characterized by defects in DNA repair lead to DNA instability |
|
|
Term
| What are some examples of common defective DNA-repair syndromes? |
|
Definition
| Hereditary nonpolyposis colon cancer (most common), xeroderma pigmentosum |
|
|
Term
| What are the characteristics of familiar cancers? |
|
Definition
| Occurs at higher frequency in affected families, increases risk 2-3x, likely depends on multiple low-penetrance alleles, often early age onset |
|
|
Term
| How does chronic inflammation contribute to the development of cancer? |
|
Definition
| Proliferating cells accumulate genetic defects due to chronic inflammation causing compensatory proliferation of cells. Can also be caused by activated immune cells releasing mediators and reactive O2 species |
|
|
Term
| What are the four classes of genes that are the chief targets of genetic damage? |
|
Definition
| Proto-oncogenes, tumor suppressor genes, genes that regulate apoptosis, DNA repair genes |
|
|
Term
| What are the key alterations seen in malignant cells? |
|
Definition
| Self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, sustained angiogenesis, ability to invade and metastasize, defective DNA repair |
|
|
Term
| What are proto-oncogenes? |
|
Definition
| Normal genes involved in cellular growth and proliferation, encodes proteins involved in replication |
|
|
Term
|
Definition
| Mutated proto-oncogenes that have the ability to promote cell growth in the absence of normal growth-promoting signals |
|
|
Term
| How do growth factors act? |
|
Definition
| Most act via paracrine signaling |
|
|
Term
| How are cancer cells associated with growth factors? |
|
Definition
| Many cancer cells acquire the ability to synthesize a growth factor to which they are responsive in an autocrine loop, most often the gene is not mutated but rather overexpressed. Some tumors have continuous receptor activation (most common) caused by mutations or overexpression |
|
|
Term
| What is the RET proto-oncogene and how is it associated with cancer? |
|
Definition
| Encodes for a growth factor receptor (RET), point mutations cause medullary thyroid carcinoma, gene rearrangement causes papillary thyroid carcinoma |
|
|
Term
| How is the epidermal growth factor receptor family associated with cancer? |
|
Definition
| ERBB1 is overexpressed in up to 80% of squamous cell carcinomas of the lung, ERBB2 is amplified in 25% of breast cancers |
|
|
Term
| What are signal transducing proteins? |
|
Definition
| Receive signals from outside the cell and transmits them to the cell's nucleus, best example of a signal transducing oncoprotein is the RAS family |
|
|
Term
| What are the characteristics of the RAS family of signal transducing proteins? |
|
Definition
| 3 RAS genes - HRAS, KRAS, and NRAS, 15-20% of all human tumors contain mutated RAS, plays an important role in signal cascades between growth factor receptors and the nucleus |
|
|
Term
| What is the most common oncogene involved in human tumors associated with transcription factors? |
|
Definition
|
|
Term
| What are the characteristics of the MYC (c-MYC oncogene)? |
|
Definition
| Proto-oncogene encodes for a transcription factor which is rapidly induced when cells receive a growth signal, oncogene codes for a mutated transcription factor |
|
|
Term
| Progression of cells through the cell cycle is orchestrated by what? |
|
Definition
| Cyclins and cyclin-dependent kinases that phosphorylate key target proteins that drive the cell cycle |
|
|
Term
| How is cyclin D or CDK4 associated with cancer? |
|
Definition
| Overexpression is common in neoplastic transformation, seen in many cancers |
|
|
Term
| What are tumor suppressor genes? |
|
Definition
| Genes that encode for products that halt or slow cell proliferation, growth-inhibitory pathways may initiate apoptosis |
|
|
Term
| What are cyclin-dependent kinase inhibitors? |
|
Definition
| CDKIs inactivate CDKs and inhibit progression through the cell cycle, down regulated by mitogenic signaling pathways, inactivation mutations frequently seen in many human malignancies |
|
|
Term
| How is retinoblastoma a model for the "two-hit" hypothesis of oncogenesis? |
|
Definition
| Two mutations involving both alleles of RB are required to produce retinoblastoma, many cases are familial in which children inherit one defective RB allele in the germ line |
|
|
Term
| Why is the G1-S checkpoint a critical step in cell division? |
|
Definition
| Passing this checkpoint causes the cell to enter the S phase, meaning they are then committed to dividing |
|
|
Term
| What is the function of the RB protein? |
|
Definition
| Regulates G1-S checkpoint of the cell cycle, blocks entry into S phase by binding to E2F |
|
|
Term
| What is the most common target for genetic alteration in human tumors? |
|
Definition
| P53 gene, homozygous loss occurs in virtually ever type of cancer |
|
|
Term
| What is the function of the P53 gene? |
|
Definition
| Transcription factor that senses cellular stress, esp. DNA damage and helps regulate response and can induce apoptosis in response to DNA damage, blocking or inactivity contributes to tumor growth |
|
|
Term
| How does loss of P53 effect clinical treatment? |
|
Definition
| Malignant neoplasms lacking P53 are relatively resistant to chemotherapy and irradiation |
|
|
Term
| Germ-line mutations in the adenomatous polyposis coli (APC) gene is associated with what? |
|
Definition
| Familial adenomatous polyposis |
|
|
Term
| What is the function of the APC gene? |
|
Definition
| Down-regulates growth promoting signals, both copies must be lost for a tumor to arise |
|
|
Term
| The INK4a/ARF (CDKN2A) gene locus encodes what protein products? |
|
Definition
| p16/INK4a which blocks cyclin mediated phosphorylation of RB and P14/ARF which activates the P53 pathway by inhibiting MDM2 |
|
|
Term
| What is the function of TGF-beta? |
|
Definition
| Potent inhibitor of proliferation, bindes to receptor for phosphorylation of R-Smads, mutation of TGF-beta is seen in all pancreatic cancers and most colon cancers |
|
|
Term
| What is the function of PTEn? |
|
Definition
| A membrane associated phosphatase, acts as a tumor suppressor by slowing the PI3K/AKT pathway which promotes cell growth and survival, germline mutations lead to Cowden syndrome, somatic mutations seen in vaious tumors |
|
|
Term
| How do tumors avoid apoptosis? |
|
Definition
| Decreased Fas expression renders tumor cells less susceptible to apoptosis by cytoxic T cells, increased FLIP production inhibits cleavage of pro-caspase-8, overxpression of Bcl-2, P53 mutations inhibit Bax expression |
|
|
Term
| How is telomerase associated with cancer? |
|
Definition
| Majority of malignant cells express telomerase for limitless replicative potetnial |
|
|
Term
|
Definition
| Vascularization of tumors, allowing them to enlarge beyond 1-2mm in diameter |
|
|
Term
| How does angiogenesis occur in neoplasms? |
|
Definition
| 3 methods: proteases by tumor cells or stromal cells release basic fibroblast growth factors, hypoxia increases HIF1-alpha which increases transcription of VEGF and bFGF genes, neoplastic cells commonly express VEGF and bFGF |
|
|
Term
| What are the two phases of the metastatic cascade? |
|
Definition
| Invasion of the ECM and vascular dissemination, homing of tumor cells, and colonization |
|
|
Term
| Extravasation of tumor emboli at distant sites involves what? |
|
Definition
| Adhesion to endothelium and basal membrane using adhesion molecules and proteases (expression of CD44 favors metastatic spread) |
|
|
Term
| What factors influence site of metastases? |
|
Definition
| Anatomic location of primary tumor, adhesion molecules present on the tumor cells, chemokine receptors expressed on the tumor cells |
|
|
Term
| Defects in which DNA repair systems are involved in the development of cancer? |
|
Definition
| Mismatch repair, nucleotide excision repair, and recombination repair |
|
|
Term
| What is hereditary nonpolposis colon cancer syndrome? |
|
Definition
| Defect in genes involved in DNA mismatch repair increasing the risk of colon cancer characterized by microsatallite instability |
|
|
Term
| What is xeroderma pigementosum? |
|
Definition
| A familial cancer syndrome with defective DNA repair, associated with multiple skin cancers, improper DNA excision repair of pyrimidine dimers caused by UV light |
|
|
Term
| How are BRCA1 and BRCA2 genes related to familial breast cancer? |
|
Definition
| Mutations account for 1/4 of familial breast cancers, gene products involve din homologous recombination of DNA repair that repairs double strand breaks |
|
|
Term
| What is the Warburg effect? |
|
Definition
| Even in the presence of ample oxygen, cancer cells shift their glucose metabolism away from oxidative phosphoryation to aerobic glycolysis |
|
|
Term
| Why does the Warburg effect increase glycolysis? |
|
Definition
| Halting oxidation of glucose at pyruvate conserves carbon to be used in anabolic pathways, principle limiting factor of cell division is the availability of carbon, not ATP |
|
|
Term
| What type of chromosomal rearrangements can activate proto-oncogenes? |
|
Definition
| Translocations and inversions |
|
|
Term
| How can translocation activate proto-oncogenes? |
|
Definition
| Overexpression by swapping its regulatory element or sequences from two different chromosomes recombining to form a hybrid gene that encodes a chimeric protein that promotes growth |
|
|
Term
| Leukemias and lymphomas tend to arise from what type of errors? |
|
Definition
| Chromosomal abnormalities |
|
|
Term
| What causes Burkitt lymphoma? |
|
Definition
| MYC gene is contiguous to regulator elements of the IgH gene, causing MYC over-expression |
|
|
Term
| What causes follicular lymphoma? |
|
Definition
| BCL2 gene becomes contiguous to regulatory elements of the IgH gene, leads to BCL2 overexpression |
|
|
Term
| What causes chronic myeloid leukemia? |
|
Definition
| ABL-BCR fusion gene encodes a constitutively active tyrosine kinase, causing cells to receive an unregulated growth signal |
|
|
Term
| Chromosomal deletion errors are most common in what type of cancers? |
|
Definition
| None-hematopoietic solid tumors, associated with loss of tumor suppressor genes |
|
|
Term
| What causes gene amplification? |
|
Definition
| Defects in DNA replication causing multiple copies of a gene and overexpression |
|
|
Term
| What are epigenetic changes? |
|
Definition
| Heritable, reversible changes in gene expression that occur without mutations, occurs either through DNA methylation or histone modifications |
|
|
Term
|
Definition
| Enzymatic component of a multiprotein complex known as polycomb repressive complex 2 which places repressive chromatin marks at the promoter of certain genes, repression leads to repression of some tumor suppressors |
|
|
Term
| EZH2 has been shown to be overexpressed in what kinds of cancers? |
|
Definition
| Breast and prostate carcinomas |
|
|
Term
|
Definition
| Short single stranded RNAs about 22 nucleotides in length, binds to complementary sequences on target mRNAs which blocks translation for post-transcriptional gene silencing, can increase or decrease expression of oncogenes or tumor suppressor genes |
|
|
Term
| Decreased expression of certain miRNAs can occur in what cancers? |
|
Definition
| Leukemias and lymphomas (increased BCL2 expression) and lung cancers (increased RAS expression) |
|
|
Term
| Individual tumors accumulate an average of how many mutant genes? |
|
Definition
|
|
Term
| What are the 2 stages of chemical carcinogenesis? |
|
Definition
| Initiation (cell exposed and DNA damaged) and promotion (cell then stimulated to proliferation. Promoters are nontumorigenic by themselves) |
|
|
Term
| Most known carcinogens are metabolized by what? |
|
Definition
|
|
Term
| The risk of skin cancer caused by UV light depends on what? |
|
Definition
| Intensity of exposure, quantity of melanin in the skin, and type of UV light |
|
|
Term
| What are the type of UV light and which one is principally responsible for the causation of skin cancer? |
|
Definition
| UVA, UVB, and UVC, UVB is usually responsible for skin cancer. UVC could cause damage but is filtered out by the ozone layer |
|
|
Term
| What are the two types of ionizing radiation? |
|
Definition
| Electromagnetic (x-rays, gamma) and particulate (alpha and beta particles) |
|
|
Term
| What are the most frequeny malignancies induced by ionizing radiation? |
|
Definition
| In descending order of frequency: leukemia, thyroid carcinoma, and lung/breast/salivary gland carcinomas |
|
|
Term
|
Definition
| A retrovirus known to cause cancer, infects CD4+ T cells and causes T cell leukemia/lymphoma |
|
|
Term
| What gives HTLV-1 its transforming ability? |
|
Definition
| The tax gene which encodes for a protein which activates transcription of seberal host cell genes involved in proliferation and differentiation of T cells, inactivates p16/INK4a and enhances cyclin D, interfereing with DNA repair and upregulating anti-apoptotic genes |
|
|
Term
| What are the different types of human papillomavirus (HPV)? |
|
Definition
| Low-risk (type 6 & 11) causes genital warts while high risk (type 16 & 18) causes carcinoma of the cervix and vulva where HPV is integrated into the host genome |
|
|
Term
| What is the Epstein-Barr virus (EBV)? |
|
Definition
| A member of the herpes family that infects B cells and some epithelial cells, involved with Burkitt lymphoma, B-cell lymphomas in immunosuppressed patients, and nasopharyngeal carcinoma |
|
|
Term
| What are the two gene products of Epstein-Barr Virus (EBV) and what are their effects? |
|
Definition
| LMP-1 is a transmembrane protein that functions as an active CD40 receptor and EBNA2 which acts as a transcription factor and upregulates cyclin D and other protooncogenes |
|
|
Term
| How does EBV cause B-cell lymphomas in immunosuppressed patients and nasopharyngeal carcinoma. |
|
Definition
| Through the expression of LMP-1 abd EBNA2 |
|
|
Term
| How is Burkitt lymphoma unique? |
|
Definition
| Only cancer caused by EBV that does not involve LMP-1 and EBNA2, instead acts as a B-cell mitogen, causing mutations and therefore lymphoma |
|
|
Term
| How does Hep B and C cause hepatocellular carcinomas? |
|
Definition
| Chronic hepatocellular injury leads to chronic inflammation and thus compensatory proliferation of hepatocytes which increases mutations and the risk for cancer. Responsible for 70-85% of hepatocellular carcinomas |
|
|
Term
| What is helicobacter pylori? |
|
Definition
| Gram-negative bacterium that causes chronic gastritis and peptic ulcers, the very first bacteria classified as a carcinogen |
|
|
Term
| How does helicobacter pylori cause gastric adenocarcinoma? |
|
Definition
| Epithelial injury induces chronic inflammation and compensatory mutations, causing mutations and cancer |
|
|
Term
| Which strains of helicobacter pylori increase the risk of adenocarcinoma? |
|
Definition
| Strains with the CagA gene which activates growth factor signal pathways in gastric epithelial cells |
|
|
Term
| How does helicobacter pylori cause Malt lymphoma? |
|
Definition
| Is a B-cell lymphoma that arises in the gastric mucosa, infects reactive T cells which stimulate a polyclonal B-cell proliferation, requires T cell stimultion, eradication of H. pylori with antibiotics can be curative |
|
|
Term
| What observation supports the idea of immune surveillance where tumor cells can be recognized by the immune system and eliminated? |
|
Definition
| Immunocompromised individuals have an increased risk of developing certain malignancies and the presences of tumor-specific T cells and anti-tumor antibodies in some patients |
|
|
Term
| What is the major immune defense mechanism against tumors? |
|
Definition
|
|
Term
| What are some examples of normal cellular proteins that may be abnormally expressed in tumor cells and then act as tumor antigens? |
|
Definition
| Tyrosinase which is normally expressed at low levels in melanocytes and MAGE antigens which are normally expressed only in gametes in the testes |
|
|
Term
| How can oncogenic viruses produce tumor antigens? |
|
Definition
| Produces proteins that are recognized as foreign by the immune system, best examples are HPV and EBV |
|
|
Term
| How do oncofetal antigens produce tumor antigens? |
|
Definition
| These are proteins that are expressed at high levels in fetal tissue and some cancer cells but not in normal adults, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) are used as tumor markers |
|
|
Term
| How do altered cell surface glycolipids and glycoproteins act as tumor antigens? |
|
Definition
| Most tumors express higher than normal levels, useful as tumor markers and targets for immunotherapy. Melanomas often express gangliosides GM2 and GD3 at high levels |
|
|
Term
| What are cell type-specific antigens? |
|
Definition
| Tumors express molecules that are normally present on the cells of origin (differentiation antigens) that are important for identifying tissue of origin as potential targets for immunotherapy. Ex. B-cell lymphomas and CD20 |
|
|
Term
| How do CD8+ T cells act as anti-tumor effectors? |
|
Definition
| Recognizes peptides from tumor Ag's which are complexed with class I MHC molecules, activated CD8+ T cells initiate apoptosis in the tumor cell. Most important effector cells against tumors |
|
|
Term
| How do natural killer cells act as anti-tumor effector mechanisms |
|
Definition
| NK cells are lymphocytes capable of killing tumor cells without prior sensitization by recognizing surface molecules induced by stress such as DNA damage, recognizes class I MHC molecules (increased expression in many tumor cells), plays an important role in eliminating tumor cells wihout class I MHC molecules |
|
|
Term
| How do macrophages act as anti-tumor effector mechanisms? |
|
Definition
| Activated T-cells and NK cell secrete IF-gamma which activates macrophages which secrete mediators that kill tumor cells |
|
|
Term
| What antibodies act as anti-tumor mechanisms? |
|
Definition
| No evidence of anti-tumor antibodies produced in vivo are protective, though administration of monoclonal antibodies directed against tumor antigens can be effective therapeutically |
|
|
Term
| By what methods do tumor cells evade immune surveillance? |
|
Definition
| Selective outgrowth of antigen negative variants, loss or reduced expression of MHC molecules, lack of costimulation of T cells, immunosuppression, and apoptosis of cytoxic T-cells |
|
|
Term
| What costimulation is necessary to activate T cells? |
|
Definition
| Presentation of peptides bound to MHC molecules and presence of costimulatory molecules such as B7-1 or CD80 which many tumor cells fail to express |
|
|
Term
| What oncogenic agents secreted by tumors may suppress the immune system? |
|
Definition
| TGF-beta, activation of CTLA4 receptors and regulatory T cells |
|
|
Term
| How do tumors induce apoptosis of cytoxic T-cells? |
|
Definition
| Some neoplasms express FasL which causes apoptosis in activated T cells |
|
|
Term
|
Definition
| A condition commonly seen in cancer patients characterized by progressive loss of body fat and lean body mass, weakness, anemia, and anorexia. 1/3 of deaths from cancer caused by cachexia |
|
|
Term
| How does cachexia differ from starvation? |
|
Definition
| Weight loss seen in cachexia results equally from loss of fat and lean muscle, basal metabolic weight is higher, is NOT caused by nutritional demands of the tumor or anorexia |
|
|
Term
| What causes cancer cachexia? |
|
Definition
| Mediators released by immune cells or tumor cells such as cytokines (esp TNF), proteolysis-inducing factor, and lipid metabolizing factor |
|
|
Term
| How is cancer cachexia treated? |
|
Definition
| Only effective Rx is removal of the tumor |
|
|
Term
| What are paraneoplastic syndromes? |
|
Definition
| Symptoms/signs in cancer-bearing individuals that cannot be explained by local invasion or distant spread of the tumor |
|
|
Term
| What causes paraneoplastic syndromes? |
|
Definition
| Tumor secreted substances and immune responses to the tumor, occurs in 10% of cancer patients, may represent earliest manifestation of an occult malignancy, may cause clinical problems/be lethal |
|
|
Term
|
Definition
| Based on the histologic appearance of the tumor, depends on degree of anaplasia, architectural features, and mitotic index |
|
|
Term
| What is the TNM staging system? |
|
Definition
| T = primary tumor, N = lymph node involvement, M = metastases |
|
|
Term
| What is of greater clinical value, staging or grading? |
|
Definition
|
|
Term
| Can tumor market assays determine the diagnosis of malignancy? |
|
Definition
| No, lack the required sensitivity |
|
|
Term
| How are cancer diagnosed histologically? |
|
Definition
| Needle biopsy, excisional biopsy, or cytologic methods (fine needle aspiration or smears from body fluids) |
|
|
Term
| How does immunohistochemistry work in the diagnosis of cancer? |
|
Definition
| Tissue section is incubated with antibody directed against an antigen of interested, then with an a tagged antibody directed against the first antibody, then incubated with a substrate for the tagging enzyme, causing a brown precipitate to form wherever the antigen of interest is present |
|
|
Term
| How is flow cytometry used in the diagnosis of cancer? |
|
Definition
| Used to measure the DNA content of individual cells and the specific surface antigens on individual tumor cells, used to assist in the diagnosis and classification of lymphomas and leukemias |
|
|
Term
| What might molecular techniques be used for in the laboratory diagnosis of cancer? |
|
Definition
| Prognosis of N-MYC gene amplification and deletions of 1p in neuroblastomas, detection of minimal residual disease or recurrence such as in ABL-BCR transcripts by PCR patients treated for CML, and the diagnoses of hereditary predisposition of cancer such as germ-line BRCA1 or BRCA2 mutations |
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