Devita, Hellman, and Rosenberg's Cancer

LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17

12 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

pathways respond to lesions created by DNA-damaging agents, such as

chemicals and radiation from numerous sources. Early discoveries in the

NER pathway were made via the study of xeroderma pigmentosa, where

patients exhibit extreme sun sensitivity. Two NER pathways have been

described: The first involves global genome scanning for lesions, and

the second detects lesions that interfere with RNA polymerases. In BER,

the repair machinery responds mainly to chemical and x-ray damage and

base loss by using DNA glycosylates to remove damaged bases and a

complex of APEX1 endonuclease, PARP, DNA polymerase/ligase, and

XRCC1 to recognize abasic sites. As of now, no inherited cancer syn-

dromes caused by mutations in BER have been discovered.

Answer 1.20. The answer is D.

DSBs can promote major cytogenetic abnormalities and are repaired via

homologous recombination or nonhomologous end-joining. ATR/CHK1

signaling leads to activation of the Fanconi anemia repair pathway.

Defects in Fanconi anemia lead to bone marrow failure, congenital abnor-

malities, predisposition to acute leukemias and squamous cell cancer, and

increased sensitivity to DNA cross-linking agents such as cisplatin and

mitomycin C.

Answer 1.21. The answer is B.

Xeroderma pigmentosa, Lynch syndrome, and Bloom syndrome are

caused by abnormalities in the nucleotide excision repair, mismatch repair,

and helicase, respectively. Fanconi anemia is caused by abnormalities in

Fancgenes, involved in the double-strand DNA repair.

Answer 1.22. The answer is A.

The mitotic spindle is central to cell division, and Aurora kinase B is

intricately involved in the process of cell division. The linking of sister

chromatids before anaphase is lost partly because of the action of Aurora

B kinase. Aurora B kinase also phosphorylates other kinetochore proteins

to aid disassembly of kinetochore-microtubule attachments not under

proper tension (as part of spindle checkpoint activation). Amplification

of Aurora B kinase has been associated with sporadic tumors.

Answer 1.23. The answer is C.

Human cancers are largely characterized by complex karyotypes with

multiple different populations. In particular, solid tumors such as lung and

colon cancer exhibit great heterogeneity that is likely the result of the high

level of genomic instability found in cancers. Some less common malig-

nancies, such as CML, are characterized by the relatively uniform pres-

ence of an abnormal karyotype, often with a limited number of detectable

breakpoints and translocations. In fact, the presence of a uniform kary-

otypic abnormality raises the possibility of a germ line cytogenetic defect

that may be further evaluated by examining the karyotype of noncancer-

ous circulating lymphocytes from the same patient. The absence of any

karyotypic abnormality in cancer cell populations is less common but