Clarification on the "orientation" of chromosomal rearrangements

Question

I need some clarifications on the concept of "orientation" in case of chromosomal rearrangements. Given a deletion event on a chromosome for example, is the resulting DNA at the breakpoint always in TH (Tail to Head) orientation? Do all duplications lead to HT orientation? And in case of translocations, inversions, etc..?

Can someone give a clear definition of "orientation", and make some examples?

Here some specific examples found in the Cosmic database:

CRC-3  large_intestine  NS  carcinoma  adenocarcinoma  intrachromosomal inversion  28066  0  2  53774826  53774826  +  2  53775947  53775947  +    21892161  

CRC-3  large_intestine  NS  carcinoma  adenocarcinoma  intrachromosomal inversion  28072  0  2  60783417  60783417  -  2  60786447  60786447  -    21892161

0006_CRUK_PC_0006_T1_DNA  prostate  NS  carcinoma  adenocarcinoma  intrachromosomal inversion  113193  0  18  60375963  60375963  +  18  77010169  77010169  -      538

0006_CRUK_PC_0006_T1_DNA  prostate  NS  carcinoma  adenocarcinoma  intrachromosomal inversion  113314  0  7  153608258  153608258  -  7  153610727  153610727  +      538

As you can see, they have inversions having all of the possible strand orientations, '++','--','+-','-+'. How is this even possible?! How to convert to H/T orientation in this case?

P.S. This is the description of the header of the data:

               HEADER[IDX] : IDX : DATA[IDX]
               Sample name :   0 : 0006_CRUK_PC_0006_T1_DNA
              Primary site :   1 : prostate
              Site subtype :   2 : NS
         Primary histology :   3 : carcinoma
         Histology subtype :   4 : adenocarcinoma
             Mutation Type :   5 : Interchromosomal unknown type
               Mutation ID :   6 : 113196
          Breakpoint Order :   7 : 0
         GRCh37 Chrom From :   8 : 6
  GRCh37 Location From min :   9 : 129148581
  GRCh37 Location From max :  10 : 129148581
        GRCh37 Strand From :  11 : -
           GRCh37 Chrom To :  12 : 7
    GRCh37 Location To min :  13 : 153610712
    GRCh37 Location To max :  14 : 153610712
          GRCh37 Strand To :  15 : -
     Non-templated ins seq :  16 : 
                 Pubmed ID :  17 : 
                  ID_STUDY :  18 : 538

Answer 1

I think the picture will help you. In fact, to determine which kind of rearrangement for the chromosomal, we need to define an "orientation". However, this orientation is not fixed. It is a definition compared with the two chromosomes before and after the rearrangement. As the picture shows, the duplicated sequence after rearrangement should be in the same orientation, if one of them not, it should be described as "inversion after duplication". For deletion, there is no difference in the orientation if the remain parts still in their previous pattern. The key point to understand, is to check the sequence before and after the rearrangement and find difference(s) between them, then compare to this picture(which is the definition of rearrangement) to find if the chromosome has one or multiple rearrangements. Hope this could help you.