Question: Need clarity on the concept of germline mutations
gravatar for inayat45shaikh
5.1 years ago by
inayat45shaikh40 wrote:

Hello everyone

I am analyzing some cancer samples wherein I have mutations have been detected from normal blood sample and tumor tissue sample of the same patient. Now I am getting mutation that are present in normal but not in tumor sample. What kind of mutation is this?? As far as i know germline mutation should be present in both normal as well as tumor sample as it is from birth and somatic is the one that is present only in tumor sample. How can we have unique mutations in normal sample. Ideally there should not be any unique mutations in normal sample. Am i thinking wrong??

sequencing snp next-gen genome • 3.4k views
ADD COMMENTlink modified 4.9 years ago by michael.d.mclellan150 • written 5.1 years ago by inayat45shaikh40

If the mutation in normal sample is heterozygous probably you're looking at LOH.

ADD REPLYlink written 5.1 years ago by poisonAlien3.0k
gravatar for trausch
5.1 years ago by
trausch1.5k wrote:

There are multiple possible reasons for "pseudo-somatic" mutations in the normal sample:

  1. Tumor's harbor somatic structural rearrangements and if, for instance, a deletion "deletes" the ALT germline SNP allele then you get a "pseudo-somatic" call in the normal sample.
  2. False positive variant calls in the normal sample that are absent in the tumor due to the random sequencing process, e.g., lack of tumor coverage.
  3. Sample processing or library preparation artifacts that weren't removed in the data processing, e.g., missed adapter sequences, failures to detect PCR artifacts or FFPE-induced mutations.
  4. Human errors (sample swaps, sample cross-contamination, etc.)
ADD COMMENTlink modified 13 months ago by _r_am32k • written 5.1 years ago by trausch1.5k
gravatar for michael.d.mclellan
4.9 years ago by
United States
michael.d.mclellan150 wrote:

If you are mostly seeing mutations in DNMT3A, TET2, JAK1, ASXL1, in older individuals - these are typical markers of clonal hematopoiesis that increase with age.

If you see odd shifts in the mutations this

If you see that the somatic variants that mostly overlap germline dbSNPs (Check you have cross contamination from other individuals.

ADD COMMENTlink written 4.9 years ago by michael.d.mclellan150
Please log in to add an answer.


Use of this site constitutes acceptance of our User Agreement and Privacy Policy.
Powered by Biostar version 2.3.0
Traffic: 1031 users visited in the last hour