THSD7B and Lung Cancer

This summary reviews the association between THSD7B and lung cancer, focusing on a familial case series where a heterozygous THSD7B variant co-segregated with disease. The evidence derives from a detailed case report of a 43‑year‑old patient with lung adenocarcinoma and four additional affected family members, supporting the contention that THSD7B mutations may contribute to familial lung cancer predisposition (PMID:36820582).

Clinical validity is considered to be in the Limited range. In the reported family, five affected individuals (the proband plus four affected relatives (PMID:36820582)) were shown to harbor the c.4000A>G (p.Ser1334Gly) THSD7B variant, providing initial evidence that this gene may be involved in lung cancer susceptibility. Although this is a single-family observation, the segregation of the variant with the disease in multiple members adds noteworthy weight to the association.

Genetic evidence is built on the observation of a heterozygous THSD7B mutation that is predicted deleterious by multiple in silico tools, including SIFT, PolyPhen2, and MutationTaster. The variant, c.4000A>G (p.Ser1334Gly), is supported by whole exome sequencing and Sanger sequencing confirmation, emphasizing its potential impact. Despite the limited number of unrelated probands, the genetic findings justify further evaluation in broader cohorts.

Functional evidence, although largely derived from computational protein structure analyses, adds important context. The mutation is associated with a marked increase in the free energy—from 8.08 kcal/mol to 68.57 kcal/mol—suggesting a significant reduction in protein stability. These experimental assessments provide mechanistic insight and support the possibility that the THSD7B alteration contributes to lung tumorigenesis through a loss-of-function effect (PMID:36820582).

Integration of both genetic and functional findings indicates that while the current evidence is restricted to a single pedigree, the deleterious nature of the THSD7B variant and its predicted impact on protein function are promising. These results underscore the potential diagnostic importance of THSD7B mutation screening, especially in families with a history of lung adenocarcinoma, although further studies are needed to confirm the association and refine risk assessment.

Key take‑home message: Early detection of THSD7B mutations in familial lung cancer cases may facilitate targeted genetic counseling and personalized diagnostic approaches.

References

• Medicine • 2023 • Identification of THSD7B and PRMT9 mutations as risk factors for familial lung adenocarcinoma: A case report PMID:36820582

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