Libre Pathology talk:Study Group

Michael's thoughts on the exam

• I wrote it and passed it in 2012. I also did the American exam the same year and passed that.
• The pass rate for the FRCPC exam is pretty high.
  • 2009-2011 it was 96+/-3.9% for Canadian medical school grads on their first attempt.

Written

• I though it was picking at details. Some things are very relevant to practise... other less so.
  • The pocketbook version of Robbins covers most of it.

Practical (slide) exam

• You should know the answer almost immediately.
  • If you don't know, write something down and move on.
• It is set to broadly cover everything.
• If it isn't a spot diagnosis... it should not be on.
• Somethings are PGY2/PGY3 stuff. One should not overthink things.
• Anecdotally, the first impression is usually the right one.
  • I think one should stick with the first impression.

Gross exam

• Go with the most probable if you're uncertain.
• I worked through the Atlas of Gross Pathology with Histologic Correlation (see Pathology books for the reference).
  • I am not sure this is necessary... but I thought it was useful.
• Flickr.com/Google images has a lot to offer in this respect.
• Gross spot diagnosis.

Forensic exam

• I thought this was tricky... and I liked forensics.
• Residents that took the exam prior to me said the same.

Cytology exam

• Some of the cases have several images.
• I remember being confused... the first three images were from one case. I remember thinking... I have the same diagnosis three times.
• Like the forensics and gross sections - this section isn't too long. From an exam strategy point-of-view, this makes it less likely that a diagnosis is repeated.

Oral exam

• I think this is to test if you are safe and useful.
  • By "safe" I mean: knowing your limits and consulting with a colleague when appropriate.
  • By "useful" I mean: you don't need to consult on everything.
• The examiners ask a pre-determined list of questions.
  • Questions may depend on one another and, in fairness, they are told to redirect you.
    • Example: You see a lung biopsy with hyaline material... and you go down the fibrosis route-- but it is really amyloidosis.
      • The examiners will say something like "how would one work-up suspected amyloid?" or "lets assume this is amyloid..."
• If you're a Canadian resident, you cannot be examined by someone within your residency program.
• As far as I know, examiners are told to be stone-faced, i.e. show no emotion.
• Some of the cases were very straight forward.
• I didn't think anything was really exotic.

Michael (talk) 23:43, 25 October 2014 (EDT)

Short answer questions on genetics and molecular pathology.

These are some questions I came up with that are plausible to me... let me know if they are out to lunch.

UNIT 1

Expand List three differences between DNA and RNA.
<left>DNA (double stranded, Thymine, deoxyribose, more stable; RNA single stranded, ribose, uracil</left>

Expand What are the three stop codons?
UAA, UGA, UAG

Expand Where does transcription begin?
promoters at the 5' end before the coding region

Expand List 2 enzymes necessary for transcription and their function.
helicase, polymerase

Expand List and describe three post transcription modifications of RNA.
Splicing, cappping, 3'polyadenylation,

Expand List three differences between somatic and germline mutations.
Microsatellite instability

Expand What is the difference between a missense and a non-sense mutation?
Microsatellite instability

Expand Define a frameshift mutation.
Microsatellite instability

Expand Why are inversion mutations difficult to detect?
Microsatellite instability

Expand Describe the potential sequelae of a translocation mutation.
Microsatellite instability

UNIT 2

Expand Translate the following: c.1524_1527delCGTA.
Microsatellite instability

Expand List 5 features of SNPs.
Microsatellite instability

Expand Define a regulatory SNP and a synonymous SNP?
Microsatellite instability

Expand What is the difference between a microstalellite and a minisattelite?
Microsatellite instability

Expand Describe Hardy-Weinberg Equilibrium?
Microsatellite instability

Expand What factors can disrupt the H-W equilibrium?
Microsatellite instability

Expand What is linkage disequilibrium?
Microsatellite instability

UNIT 3

Expand What are the three major steps of PCR?
Microsatellite instability

Expand What is the hallmark of PCR?
Microsatellite instability

Expand What factors affect the method of genotyping chosen?
Microsatellite instability

Expand Define sensitivity, specificity, positive predictive value and negative predictive value.
Microsatellite instability

Expand Define reproducibility and accuracy of an analytical test.
Microsatellite instability

Expand Describe briefly Sanger sequencing.
Microsatellite instability

Expand Describe briefly how Taqman automated genotyping is used for allele detection.
Microsatellite instability

Expand How are DNA microarrays used to identify drug disposition or responses?
Microsatellite instability

UNIT 4

Expand Describe the procedure for submitting FFPE slides for KRAS for colorectal cancer.
Microsatellite instability

Expand Compare and contrast uniplex versus multiplex genotyping.
Microsatellite instability

Expand Compare and contrast conventional vs massively parallel sequencing.
Microsatellite instability

Expand What is multiplex ligation-dependent ligation (MLPA)?
Microsatellite instability

Expand What is fragment analysis?
Microsatellite instability

Expand Compare and contrast RT-PCR vs qRTPCR.
Microsatellite instability

Expand What is MSI?
Microsatellite instability

Expand What is methylation analysis?
Microsatellite instability

UNIT 5

Expand What are the four test features required to be documented by the CLIA?
Microsatellite instability

Expand What are "in vitro diagnostics" vs "laboratory developed tests"?
Microsatellite instability

Expand What does validation mean?
Microsatellite instability

Expand What are the four performance characteristics that need to be verified for FDA cleared/approved tests?
Microsatellite instability

Expand What are the six performance characteristics that need to be verified for FDA cleared LDTs or modified FDA cleared/approved tests?
Microsatellite instability

UNIT 6

Expand List the components of a molecular pathology report.
Microsatellite instability

Expand Define analytical sensitivity and clinical sensitivity.
Microsatellite instability

Expand What should be said in a report of a molecular test on a patient for residual disease if no previous positive assay was confirmed?
Microsatellite instability

Expand Define ammended report versus addendum report.
Microsatellite instability

Expand Whose responsibility is it to sythesize the test results with other clinico-pathological information?
Microsatellite instability

Expand How long are cytogenetic reports required to be kept by CAP?
Microsatellite instability

Expand What is the recommended process to use test results if an assay is not yet validated for clinical use?
Microsatellite instability

Expand Give three examples of "grey areas" which warrant discretion of professionals involved to use a non-validated test?
Microsatellite instability

Expand What reference standard is available for gene nomenclature?
Microsatellite instability

Expand Create a table of the most common gene rearrangements associated with heme and soft tissue diseases.
Microsatellite instability

Expand What is a "DNA fingerprint" and what can it be used for?
A method that examines multiple areas of short tandem repeats to identify paternity, mosaicism, chimerism, and identity in forensics cases

Robbins and Cotran Chapter 5 9th Edition:

Expand MC cause of spontaneous abortion is ?
A demonstrable chromosomal abnormality.

Expand 1% of all newborn infants possess a gross chromosomal abnormality and 5% of people <25y present with
a genetic disease.

Expand Mutation
permanent change in the DNA, if affect germ cells are transmitted to the progeny

Expand List and describe 4 broad categories of human genetic disorders:

[[Disorders related to mutation sin single genes with large effects i. Usually follow classic Mendelian pattern of inheritance ii. Often highly penetrant (large proportion of pop with gene has disease) b. Chromosomal disorders i. Structural or numerical alterations in autosomes and sex chromosomes ii. Uncommon, high penetrance c. Complex multigenic disorders i. Interactions between multiple variant forms of genes and environmental factors (polymorphisms), poly genic means disease when many polymorphism present d. Single gene disorders with nonclassic patterns of inheritance (not mendelian) i. Disorders resulting from triplet repeat mutations ii. Mutations in mitochondrial DNA iii. Those influenced by genomic imprinting iv. Those influenced by gonadal mosaicism]]

Expand List and describe the possible outcomes of a point mutation in a coding region?
[[a. Missense mutation – pt mutation changes amino acid code, conservative when the amino acid is preserved, non conservative when replaced with another amino acid b. Nonsense mutation – makes a stop codon ]]

Expand List and describe the possible outcomes of point mutation or deletion in a non-coding region.
[[a. Promoters/enhancers – interfere with binding of transcription factors, marker reduction or total lack of transcription, b. Introns – defective splicing > failure to make mature RNA > no translation]]

{{hidden|List and describe the possible outcomes of deletions and insertions.|

[[a. Small coding: not multiple of three = frameshift, if multiple of 3 than add or del amino acids accordingly, often premature stop codon

i. Tay Sachs disease: 4 base pair insertion in Hexosaminidase A gene {{hidden|List and describe the possible outcomes of trinucleotide repeat mutations. a. Usually G&C, dynamic and increase during gametogenesis, “RNA stutters” b. Fragile X – CGG 250-4000, Huntinton’s Disease * See Neuropath Notes

Expand {{{1}}}
{{{2}}}

Stopped at P142

Molecular Genetic Diagnosis 1. List three basic molecular diagnostic techniques a. Karyotyping b. Southern blot c. Sanger DNA sequencing d. Polymerase chain reaction 2. Constitutional vs somatic mutations.

Hi Michael, I've started, but mostly just with the questions for now, as I study I will keep working on it. Can you help me, maybe we can make additional discussion pages for each of my "study" exams,e.g. molecular, robbins chapters, cap protocols etc. This is just like LaTEX!!!