Devita, Hellman, and Rosenberg's Cancer

LWBK1006-02 LWW-Govindan-Review November 24, 2011 11:18

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

Answer 2.6. The answer is A.

TGF-is a cytokine that binds to a class of transcription factors known as

SMADs that translocate to the nucleus, where they complex with DNA-

binding transcription factors and coactivators to transactivate specific

genes. IFNs are another class of cytokines that have antiproliferative

effects by means of upregulation of CDK inhibitors and downregulation

of cyclins. INK family proteins are CDK inhibitors of which p15 specif-

ically inhibits CDK4 and CDK6 directly and cyclin E-CDK2 and cyclin

A-CDK2 indirectly. The final outcome of antimitogenic signaling involves

the upregulation of CDK inhibitors and downregulation of cyclins.

Answer 2.7. The answer is A.

MicroRNAs regulate mRNA expression by degradation or inhibition of

translation. Some of them target mRNA encoding cell-cycle regulatory

proteins but none of them directly encode proteins that regulate cell cycle.

Answer 2.8. The answer is B.

All of these genes are involved in regulation of cell cycle. TheNBS1gene

regulates checkpoints in cell cycles and also is involved in DNA repair.

Mutation involving theNBS1gene results in the Nijmegen breakage syn-

drome 1. Patients diagnosed with this syndrome have increased risk of

developing non-Hodgkins lymphoma.

Answer 2.9. The answer is C.

Secondary to the topology of telomeres and the requirements of DNA

replication, each cell cycle causes progressive shortening of the telom-

eres. In most, if not all, somatic cells, when sufficient telomere attrition

has been reached, cells enter into a chronic checkpoint response, which

is the molecular basis of senescence. Germ line cells forego this check-

point by means of a special replicase, telomerase. For a somatic cell to

undergo malignant transformation, the senescence barrier must be over-

come allowing for unlimited proliferative capacity.

Answer 2.10. The answer is D.

Tumor suppressor genes usually encode negative regulators of growth

and proliferation, thereby conferring protection to cells against malig-

nancy. Protooncogenes encode genes in which mutations may cause gain

of function or an enhanced level of function leading to malignancy. Muta-

tions of both tumor suppressor genes and protooncogenes may lead to

uncontrolled proliferation and malignancy.

Answer 2.11. The answer is A.

Li–Fraumeni syndrome is caused by an inherited mutation in TP53, the

gene encoding the checkpoint effector p53. Nijmegen disease is caused by

mutation of the gene encoding Nbs1, which is required for the activation

of Chk1 and Chk2 kinases. This disease is characterized by microcephaly,