Devita, Hellman, and Rosenberg's Cancer

LWBK1006-03 LWW-Govindan-Review November 24, 2011 11:19

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

genes, which then can lead to devastating consequences resulting in dis-

tinct outcomes in distinct tissues. The haploinsufficient tumor suppressors

contrast with the retinoblastoma paradigm or the Knudson’s hypothesis.

In retinoblastoma, individuals inherit a mutation in one of the alleles of

the RB gene and require a “second hit” to the other allele to develop

cancer.

Answer 3.20. The answer is A.

Among the animal viruses, retroviruses are unique in having an RNA

genome that replicates through a DNA intermediate. Once the retrovirus

infects the cell, the single-stranded viral genome is converted to double-

stranded DNA by an RNA-dependent DNA polymerase or reverse tran-

scriptase. The double-stranded DNA then is integrated into a host cell

chromosome. Retroviruses in animals can transform the infected cell by

integrating the viral DNA close to cellular oncogenes, integrating a pro-

tooncogene in the host cell genome, or altering the cellular gene expres-

sion or function. In humans, HTLV1 is the only retrovirus that has been

shown to have a direct transforming effect. HIV, the other retrovirus,

is more likely to cause malignant transformation in humans through an

indirect effect of immune suppression.

Answer 3.21. The answer is D.

Retroviruses transform cells through either an acute process or a slow

transforming process. Acutely transforming viruses insert a viral oncogene

into the host cell genome leading to malignant transformation. The slowly

transforming viruses cause cellular transformation either by inserting the

viral DNA adjacent to a cellular protooncogene (insertional mutagenesis)

or altering the expression of cellular gene expression and function by

viral proteins. Inflammation and its consequences are not known to be

an important cause of retrovirus-induced cellular transformation.

Answer 3.22. The answer is A.

HTLV-1 shares a number of features with HIV: a complex genetic struc-

ture, tropism for CD4 T lymphocytes, induction of syncytia in cultured

T cells, and similar routes of transmission (blood transfusions, sexual con-

tact, needle sharing, and breastfeeding). However, HTLV-1 infection is not

associated with marked cellular immunodeficiency unless ATL develops.

Unlike HIV, where infection by free virions is typical, with high levels

of viremia detected in HIV-1-infected individuals, a significant viremia is

not detected in individuals with HTLV-1. In patients with HTLV-1, the

virus spreads to uninfected cells by cell-to-cell transmission of the virus.

In addition, the number of HTLV-1-infected cells within an individual

increases by simple mitosis of virus-containing T cells.

Answer 3.23. The answer is C.

HTLV1 protein Tax activates viral gene expression by interacting with cel-

lular transcription proteins. Subsequently through this interaction with

cellular transcription proteins, Tax leads to activation of several cellular