The Molecular Hematology Gym

Question 1:

The vast majority of BCR-ABL breakpoints in CML are positioned within the major breakpoint cluster spanning from exon 13-15, and these code for the p210 protein - True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 1:
True. See Krumbholz et al.

+++++++++++++++++++++++++++++++++++++++++++++++

Question 2:

BCR-ABL fusions in ALL usually occur in the minor BCR (m-BCR) in intron 1, resulting in a p190 protein - True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 2:
True. See Krumbholz et al.

+++++++++++++++++++++++++++++++++++++++++++++++

Question 3:

e13a2 = b2a2 in older nomenclature

e14a2 = b3a2 in older nomenclature

True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 3:

True. See Hijiya et al.

+++++++++++++++++++++++++++++++++++++++++++++++

Question 4:

The e13a2 (b2a2)/ e14a2 (b3a2) fusion transcripts encode for a 210-kDa protein, whereas the e1a2 encodes for a 190-kDa protein, and the e19a2 encodes for a 230-kDa protein.

True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 4:

True. See Verma et al.

The e13a2 (b2a2)/e14a2 (b3a2) fusion transcripts encode for a 210 kDA protein, whereas the e1a2 encodes for a 190 kDA protein, and the e19a2 encodes for a 230 kDa protein.

+++++++++++++++++++++++++++++++++++++++++++++++

Question 5:

The first chromosomal translocation to be identified in acute myeloid leukemia was that of chromosome 8 and 21.

True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 5:

True.

Rowley 1998.
Rowley 1973

+++++++++++++++++++++++++++++++++++++++++++++++

Question 6:

The ETO gene stands for (eight, twenty one).

True/False?

+++++++++++++++++++++++++++++++++++++++++++++++

Answer 6:
True
Rowley 1998
pg 507

+++++++++++++++++++++++++++++++++++++++++++++++

Question 7:

With regards to BCR-ABL fusions, which exons span the major breakpoint cluster region (M-bcr)?

a. e1

b. e2

c. e3

d. e4

e. e5

f. b1

g. b2

h. b3

i. b4

j. b5

k. a1

l. a2

m. a3

n. a4

o. a5

Answer: f-j

See Melo; The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype

++++++++++++++++++++++++++++++

   Question 8:

According to Professor Weatherall, why was severe form of thalassemia first described in the USA, where they were very uncommon, and not in a Mediterranean country where they must have occurred at a very high frequency?

a. Access to technologies

b. Severe thalassemia would not have been recognized as a distinct entity in the Mediterranean countries since the presentation overlaps with malaria (severe anemia and splenic enlargement)

Answer:

b (pg 18, Thalassemia - The Biography)

+++++++++++++++++++++++++++++

The Molecular/Genomic Diagnostics Gym

Question 1

Commonly used metrics and quality control parameters used to assess run performance for NGS wet bench process documentation include:

A. Percentage of reads mapping to the target region
B. Fraction of bases meeting specified quality and coverage thresholds
C. Average coverage per base

+++++++++++++++++++++++++++++++++++++

Answer 1

All of the above.

See Aziz et al. (College of American Pathologists’ Laboratory Standards for Next-Generation Sequencing Clinical Tests APLM 2014)

+++++++++++++++++++++++++++++++++++++

Question 2

Essential performance characteristics that need to be determined during internal validation include:

A. Analytic sensitivity
B. Analytic specificity
C. Accuracy
D. Precision
E. Limit of detection

+++++++++++++++++++++++++++++++++++++

Answer 2

All of the above.

See Aziz et al. (College of American Pathologists’ Laboratory Standards for Next-Generation Sequencing Clinical Tests APLM 2014)

+++++++++++++++++++++++++++++++++++++

Question 3

According to the framework proposed by the ACCE, genetic tests should be evaluated on which of the following criteria:

A. Analytical validity
B. Clinical validity
C. Clinical utility
D. Ethical, legal and social issues

+++++++++++++++++++++++++++++++++++++

Answer 3

All of the above.

See Easton et al. (NEJM 2015)

+++++++++++++++++++++++++++++++++++++

Question 4

In vitro diagnostics that have gone through and passed a 510(k) trial are considered FDA-approved - True/False

+++++++++++++++++++++++++++++++++++++

Answer 4

False. FDA-cleared.

See Halling et al. (APLM 2012)

+++++++++++++++++++++++++++++++++++++

Question 5

"Verification" and "validation" pertain to FDA-approved/cleared and laboratory-developed tests respectively - True/False

+++++++++++++++++++++++++++++++++++++

Answer 5

True.

See Halling et al. (APLM 2012)

+++++++++++++++++++++++++++++++++++++

Question 6

The mnemonic PARR+AS+AS is most relevant to FDA-approved/cleared tests - True/False

+++++++++++++++++++++++++++++++++++++

Answer 6

False. LDT.

PARR for FDA-approved/cleared tests.

See Halling et al. (APLM 2012)

+++++++++++++++++++++++++++++++++++++

Question 7

Professional organizations or state agencies demonstrating that their accreditation requirements meet or exceed those specified by CLIA have "deemed status" from CMS (Centers for Medicare 7 Medicaid Services) to accredit laboratories - True/False

+++++++++++++++++++++++++++++++++++++

Answer 7

True.

See Jennings et al. (APLM 2009)

+++++++++++++++++++++++++++++++++++++

Question 8

When applied to qualitative tests, "accuracy" is equivalent to "sensitivity and specificity" - True/False

+++++++++++++++++++++++++++++++++++++

Answer 8

True.

See Jennings et al. (APLM 2009)

+++++++++++++++++++++++++++++++++++++

Question 9

True/False: Although the terms depth and coverage can be used interchangeably, coverage has also been used to denote the breadth of coverage of a target genome.

+++++++++++++++++++++++++++++++++++++

Answer 9

True.

See Sims et al. (Sequencing depth and coverage: key considerations in genomic analyses, 2014)