Combined linkage and association analysis of classical Hodgkin lymphoma

Abstract

The heritability of classical Hodgkin lymphoma (cHL) has yet to be fully deciphered. We report a family with five members diagnosed with nodular sclerosis cHL. Genetic analysis of the family provided evidence of linkage at chromosomes 2q35-37, 3p14-22 and 21q22, with logarithm of odds score >2. We excluded the possibility of common genetic variation influencing cHL risk at regions of linkage, by analysing GWAS data from 2,201 cHL cases and 12,460 controls. Whole exome sequencing of affected family members identified the shared missense mutations p.(Arg76Gln) in FAM107A and p.(Thr220Ala) in SLC26A6 at 3p21 as being predicted to impact on protein function. FAM107A expression was shown to be low or absent in lymphoblastoid cell lines and SLC26A6 expression lower in lymphoblastoid cell lines derived from p.(Thr220Ala) mutation carriers. Expression of FAM107A and SLC26A6 was low or absent in Hodgkin Reed-Sternberg (HRS) cell lines and in HRS cells in Hodgkin lymphoma tissue. No sequence variants were detected in KLHDC8B, a gene previously suggested as a cause of familial cHL linked to 3p21. Our findings provide evidence for candidate gene susceptibility to familial cHL.

Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma

“…In a previous mutational analysis carried in colorectal cell lines, SLC26A6 was found to be mutated in >10% of the 23 colorectal cancer cell lines, suggesting that SLC26A6 might play a significant role in colorectal cancer ( 23 ). Nevertheless, in another study, protein-disrupting mutations in SLC26A6 was found in familial classical Hodgkin lymphoma (cHL) individuals, implying that SLC26A6 silencing might associate with the risk of cHL ( 24 ). In this study, we found that overexpressed SLC26A6 associated with poor survival in HCC patients, and its knockdown inhibited the malignant phenotype of HCC cells, demonstrating that SLC26A might serve as an oncogene in HCC tumorigenesis.…”

“…In colorectal cancer, SLC26A6 was reported to be mutated in over 10% of the 23 colorectal cancer cell lines ( 23 ). Moreover, genetic analysis revealed that SLC26A6 mutation might associate with Hodgkin lymphoma, and SLC26A6 expression was low or absent in Hodgkin lymphoma cells ( 24 ). However, little is known about the role of SLC26A6 in tumorigenesis, especially in HCC.…”

Tumor mutation burden (TMB)-associated signature constructed to predict survival of lung squamous cell carcinoma patients

“…Katarzyna Kiwerska et al found that the expression of FAM107A was reduced significantly in larynx squamous cell carcinoma (LSCC) 20 , and the recurrent inactivation of FAM107A may be involved LSCC development. FAM107A expression was low or even absent in Hodgkin Reed-Sternberg (HRS) cells 21 . IGLL1 is part of the immunoglobulin gene superfamily, and its expression is closely related to humoral immunity 22 .…”

The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics

“…It is also known as Tohoku University cDNA clone A on chromosome 3 (TU3A) or Family with sequence similarity 107, member A (FAM107A) [24,25]. DRR1 is downregulated in various cancer cell lines, including renal cell, ovarian, cervical, laryngeal, gastric, prostate, liver, lymph, and non-small cell lung cancer and is associated with the progression of neuroblastoma, meningioma and malignant glioma [26,27,28,29,30,31,32,33,34,35,36]. On the other hand, DRR1 is highly expressed in outer radial glial cells [37] and in the invasive component of glioblastoma [38,39].…”