LWBK1006-01 LWW-Govindan-Review November 24, 2011 11:17
10 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review
Answer 1.11. The answer is C.
The term “proteome” is generally taken to refer to all potentially
expressed proteins encoded by the genome. However, many operational
definitions specify only those proteins expressed at a given time or under
certain conditions, so answer “A” denotes a relatively common use of
the term as well. Increasingly, the term “proteome” is used in conjunc-
tion with a modifier such as “serum,” cellular,” or even “malignant” to
denote a more limited set of conditions. Protonation is a preparative step
before proteomic evaluation by current means. Most proteomic analyses
require cleavage of the proteins in the samples followed by protonation of
the resulting peptides before matrix-assisted laser desorption ionization-
time of flight analysis.
Answer 1.12. The answer is A.
Current gene array technology is focused mostly around the detec-
tion of gene transcript levels. Small quantities of nuclear material from
minimal biopsy material can be amplified via polymerase chain reac-
tion. However, protein–protein interactions and posttranslational pro-
cessing cannot be predicted. Multiple technologies have been used
to detect “proteomic signatures,” which include two-dimensional gel
electrophoresis, affinity tagging, liquid chromatography coupled with
mass spectrometry, and antibody arrays. Limitations of proteomic tech-
nologies include disruption of the native three-dimensional protein
conformations in addition to the need for larger amounts of biopsy
material needed compared with genomic arrays. This requires sen-
sitive proteomic technology, such as antibodies in the femtomolar
range.
Answer 1.13. The answer is B.
The term “peptidome” refers to the low-molecular-weight range of the
proteome that consists of peptides or protein fragments generally less
than 50,000 daltons. It is thought that these peptide fragments are
secreted from various tumors and exist in the circulation bound to car-
rier proteins. Studies are under way to determine if the secreted pattern
of such fragments can be correlated with disease states. A confound-
ing factor in peptidome analysis may be the susceptibility of peptides
to protease degradation in the blood after secretion from the tumor. It
remains to be seen if consistent patterns can be determined after protease
degradation.
Answer 1.14. The answer is C.
HNPCC is associated with a 60% to 80% lifetime risk of developing
colorectal cancer and accounts for 2% to 5% of all cases of colorectal
cancer. In both sporadic and HNPCC cases, microsatellite instability has
been associated with a more favorable prognosis but potential resistance
to 5-fluorouracil chemotherapy.