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Fusion genes should have an origin.These are essentially hybrid genes that are translocated in its entirety. Eg. BCR-ABL, EML4-ALK are known to be implicated in cancer pathogenesis. Do these translocation events occur somatically or is there a possibility for it to be inherited?

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  • $\begingroup$ What do you mean by fusion genes? Can you please add some context? At the moment it is unclear what you are trying to ask. $\endgroup$ – WYSIWYG May 15 '19 at 11:54
  • $\begingroup$ Hybrid genes that are translocated in its entirety. Eg. BCR-ABL, EML4-ALK are known to be implicated in cancer pathogenesis. Do these translocation events occur somatically or is there a possibility for it to be inherited? $\endgroup$ – Aishwarya Parasuram May 15 '19 at 12:10
  • $\begingroup$ Hi and Welcome to Stack exchange. I think your question is not properly phrased. These hybrid genes you mention are indeed related to carcinogenesis, as in they are mutations commonly found in specific cancer types. It is unclear whether you are asking if (any) translocation events can also occur in the germline, or whether cancer-associated translocation mutations (such as the Bcr-Abl, Tpr-Met or Gag-Onc) can occur in the germline, and thus be inherited. $\endgroup$ – Athe May 16 '19 at 11:48
  • $\begingroup$ Thank you. Sorrry if it wasn't clear. I'm asking if cancer-associated translocation mutations (such as the Bcr-Abl, Tpr-Met or Gag-Onc) can occur in the germline, and thus be inherited. ?If yes, do you have papers supporting this? I haven't been able to find germline origin fusion genes. $\endgroup$ – Aishwarya Parasuram May 17 '19 at 7:47
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There is at least one (possible) description of an inherited (aka germline) fusion gene: KANSARL. See the paper "Identification of KANSARL as the first cancer predisposition fusion gene specific to the population of European ancestry origin" by Zhou, Yang, Ning et al., Oncotarget. 2017; 8:50594-50607.

KANSARL fusion gene is familially inherited and may be ubiquitously expressed in KANSARL-bearing individuals The presence of KANSARL fusion transcripts in normal and adjacent tissues in CGD and VPD raised the possibility that KANSARL fusion transcripts are derived from a germline-inherited fusion gene. To investigate this possibility, we performed RNA-seq data analysis for the lymphoblastoid cell lines derived from the families in the CEU population (CEPH/Utah Pedigree 1463, Utah residents with ancestry from northern and western Europe), which includes a three-generation family with 17 individuals [47]. Supplementary Table 9 and Supplementary Figure 8 show that KANSARL fusion transcripts were detected in 15 of 17 family members, as indicated by black squares and circles in Supplementary Figure 8, except son (NA12885), which is deviated from the first Mendel law. A reasonable explanation is that the grandfather sample (NA12889) might have been mixed with the son sample (NA12885). To prove this possibility, we performed analyses of the WSG data (PRJEB3381) and RNA-seq from 1000 Genome Project, and shown that both WSG and RNA-seq of grandfather sample (NA12889) are KANSARL-negative while WGS of the son (NA12885) is KANSARL-positive (Supplementary Table 10). Supplementary Table 10 shows the genomic breakpoint 1 and 2 of the KANSARL fusion gene (Supplementary Figure 5 and 9) identified by analysis of WGS data among some members of CEPH/Utah Pedigree 1463. Therefore, Both WGS and RNA-seq data support that the father (NA12877) and the mother (NA12878) have the genotypes of KANSARL-/KANSARL- and KANSARL+/KANSARL+ respectively and all their offsprings are the genotype KANSARL+/KANSARL-

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