Exam 20: Cancer

Myelomas are cancers of blood plasma cells-white blood cells that are normally responsible for producing large quantities of antibodies. In the following "Circos plot" for myelomas in a hypothetical mammalian genome, the interchromosomal rearrangements are indicated by red lines and variations in copy numbers are indicated in blue. The positions of named genes are indicated with arrows. On which chromosome do you expect to find the antibody genes? Write down the chromosome number (1 to 5) as your answer.

Which of the following is estimated to be the leading cause of death from cancer in the United States?

Indicate true (T) and false (F) statements below regarding the properties of cancer cells. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancer cells invade and colonize territories that normally belong to other cells. ( ) Unlike in normal tissues, cell death is extremely rare in tumors. ( ) Cancer cells grow and proliferate in defiance of normal restraints. ( ) Malignant tumors are composed of cells that grow and proliferate, but still have not acquired invasiveness.

Indicate true (T) and false (F) statements below regarding cancer. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Cancers become less and less heterogeneous as they progress. ( ) Knocking out Ras or Myc genes individually leads to a higher incidence of cancers in mice, and knocking out both genes simultaneously has an even stronger phenotype. ( ) Wnt signaling is important in colon epithelial cells and, correspondingly, mutations in genes in the Wnt pathway are present in most colorectal cancers. ( ) Genome destabilization in a subset of colorectal cancers that have defects in DNA mismatch repair takes the form of chromosome breaks, translocations, and deletions.

The effect of the deletion of one copy of the gene encoding p53 is different from the effects caused by other p53 mutations. For example, some loss-of-function mutations in the DNA-binding domain of p53 cripple its function as a transcription regulator. Such a mutation in only one copy of the p53 gene can be enough to confer a p53 loss-of-function phenotype, even when the other copy of the gene on the homologous chromosome is wild type. This is because …

You are studying the rising incidence of a certain subtype of cervical cancer in Oceania, and are curious to know whether environmental factors are the dominant cause of the disease. You collect the incidence statistics from indigenous populations as well as from two different immigrant populations in three different countries, as shown in the following table. Do these data appear to be consistent with a dominant role of environmental risk factors (E) or a genetic background (G) for this type of cancer? Write down E or G as your answer.

X-chromosome inactivation in female mammals occurs mostly randomly early in development, resulting in a heterogeneous cell population, with each cell having inactivated one or the other of its X chromosomes and passing on the same X-inactivation choice to its offspring. The inactivated X chromosome is generally hypermethylated and transcriptionally inactive. You are studying a newly discovered type of colon tumor in women that has a morphology distinct from that of other colon adenomas. You extract chromosomal DNA from the tumor cells. You then either keep the DNA untreated, or digest the DNA with a methylation-sensitive restriction enzyme that only cleaves its recognition DNA sequence if the sequence is not methylated. Finally, you amplify by polymerase chain reaction (PCR) a locus on the X chromosome known to be polymorphic in length (i.e. it is expected to be of different sizes in different X chromosomes). The locus has a restriction site for the mentioned enzyme, such that cleavage would prevent PCR amplification. You quantify the amount of PCR products corresponding to shorter and longer versions of the locus, and obtain the results shown in the following table. Do these data appear to be in better agreement with a monoclonal (M) or a polyclonal (P) origin of cancer? A monoclonal origin would mean that all cells in the tumor are the clonal descendants of a single abnormal cell, while a polyclonal tumor is composed of cells from different lineages. Write M or P as your answer.

According to the cancer stem-cell model for tumor growth and propagation, …

Three fundamental controls seem to have been subverted in essentially every type of cancer. Choose these three among the following regulatory axes. Your answer would be a three-letter string composed of letters A to F only, in alphabetical order, e.g. BDF. (A) Wnt pathway (B) Rb pathway (C) RTK/Ras/PI3K pathway (D) p53 pathway (E) Hippo pathway (F) GPCR/PKA pathway

Carcinoma of the uterine cervix in humans …

Once the molecular aberrations in a cancer are understood, drugs can be designed with a rational approach to treat the cancer. Which of the following is NOT true regarding such drugs?

Indicate whether each of the following descriptions better applies to a cancer cell (C) or a normal adult cell (N). Your answer would be a four-letter string composed of letters C and N only, e.g. CCNC. ( ) Higher lactate production ( ) Higher oxidative phosphorylation ( ) Contact inhibition ( ) Anchorage independence

In the following simplified diagram of cell divisions in a multicellular species, the germ-cell and somatic-cell lineages are depicted. Which of the indicated cells (1 or 2) represents the germ line? Write down 1 or 2 as your answer.

A benign neoplasia of cartilage is called a …

Which of the following sequential barriers to metastasis is the easiest to overcome for cancer cells in general?

Most DNA tumor viruses inhibit the products of …

Indicate whether each of the following viruses is mostly associated with cervical cancer (C), Kaposi's sarcoma (K), liver cancer (L), or stomach cancer (S). Your answer would be a four-letter string composed of letters C, K, L, and S, e.g. CKLS. ( ) Hepatitis-B virus (HBV) ( ) Human immunodeficiency virus (HIV) ( ) Human papillomavirus (HPV) ( ) Helicobacter pylori

Carcinoma cells that have acquired malignancy and started local invasiveness to begin metastasis …

The homologous chromosome pairs in our cells do not carry identical sequences in all loci. This heterozygosity (difference between the two copies) can be altered in cancer: in fact, loss of heterozygosity at many loci is observed in cancer cells, through an increase in either homozygosity (two identical copies) or hemizygosity (i.e. loss of one copy). Researchers can take advantage of this loss of heterozygosity in cancer cells to identify genomic loci that contain cancer-critical genes. What type of gene would you expect to find in chromosomal regions with a loss of heterozygosity? Proto-oncogenes (P) or tumor suppressor genes (T)? Write down P or T as your answer.

Indicate true (T) and false (F) statements below regarding colorectal cancers. Your answer would be a four-letter string composed of letters T and F only, e.g. TFFF. ( ) Observation of polyps in the colon epithelium of a patient is an indication of a malignant carcinoma. ( ) Progression of colorectal cancer is very slow and normally takes over 10 years to turn into malignancy. ( ) Colorectal cancers are usually diagnosed later in life. ( ) Invasive colorectal cancer cells usually metastasize to lymph nodes via lymphatic vessels and then into the bloodstream.