Portfolio Media. Inc. | 230 Park Avenue, 7th Floor | New York, NY 10169 | www.law360.

com
Phone: +1 646 783 7100 | Fax: +1 646 783 7161 | customerservice@[Link]

What Gene Findings Mean For Asbestos Mesothelioma

Claims
By David Schwartz and Kirk Hartley (May 29, 2025, 5:20 PM EDT)

Recent advances in genetic research have provided substantial evidence that

could prove to be pivotal in asbestos-related malignant mesothelioma, or MM,
litigation. A study published in January in Scientific Reports by Dahlia Nielsen
and colleagues could fundamentally change how defendants approach
mesothelioma litigation.[1]

The new research provides compelling statistical evidence that certain

inherited genetic mutations alone — specifically, pathogenic mutations of the
BAP1 gene — can cause MM independent of asbestos exposure, a finding that
contradicts long-held assumptions about MM causation.

This finding supports what some leading researchers have long suspected: that David Schwartz
genetic factors may account for a significant portion of MM cases, independent
of environmental exposures.

This finding could shift the focus from external factors like asbestos to
inherited genetic factors in a significant number of MM cases across the
country — with the most impact in venues and cases in which some plaintiffs
counsel have argued that genetic abnormalities cannot by themselves cause
mesothelioma or other cancers.

The Nielsen study is especially notable from a mesothelioma litigation

perspective, because focusing on genetic causation evidence in mesothelioma
cases has been late to arrive when compared to other types of personal injury
lawsuits. Kirk Hartley

For example, in 2006, genetic sequencing evidence resulted in the Delaware Supreme Court's
affirmation of summary judgment for the defense in Bowen v. E.I. DuPont de Nemours & Co., a
fungicide exposure case.[2] There, the genetic evidence showed that deformities in children were in
fact caused by inherited, or germline, mutations that caused a rare disorder.

In addition, orders approving genetic testing with no limits on genes to be tested were previously
entered in multiple state court benzene cases.[3] And the U.S. Court of Appeals for the First Circuit
extensively addressed genetic causation evidence in a benzene case, Milward v. Acuity Specialty
Products Group, in 2011.[4]

Similarly, for several decades, orders for genetic sequencing have often been entered in cases
alleging that a child's disabilities were caused by medical malpractice before or during birth, including
in Harris v. Mercy Hospital, a 1992 Illinois intermediate appellate court ruling affirming a trial court's
genetic testing order,[5] and in Cruz v. Superior Court, a 2004 case in California's Fourth Appellate
District Court.[6]

More recently, in Ortega v. U.S., a judge in the U.S. District Court for the Northern District of Illinois
entered summary judgment in 2021 for medical malpractice defendants that relied on genetic testing
data that the plaintiff's expert failed to meaningfully address.[7]

Orders for genetic testing also have been deemed appropriate in a wide range of circumstances by
commentators with expertise in both genetics and law, provided that a moving defendant has made a
reasonable showing of facts suggesting the presence of potentially causative genetic abnormalities.
[8]

The findings in the Nielsen study and some other recent studies should cause both plaintiffs and
defense counsel to carefully assess the positions they present through expert testimony regarding
genetic causation of cancers and other phenotypes.

As noted above, some plaintiffs counsel have opposed genetic testing by arguing that genetic
abnormalities cannot by themselves cause a mesothelioma or other cancer. Outside of California,
those arguments have very seldom succeeded.

Instead, orders like the February 2018 order in Bailey v. Autozone Inc. in the Circuit Court for
Lawrence County, Tennessee, have allowed genetic sequencing with no limits on genes sequenced.[9]
Likewise, in Cole v. Honeywell, in the Circuit Court for Morgan County, Missouri, the parties stipulated
to genetic testing with no limits on genes sequenced.[10]

And in cases such as Holsten v. Amalgamated Sugar Co., in the Circuit Court for Madison County,
Illinois, the plaintiff withdrew opposition to genetic testing and turned over tissue for unlimited
sequencing.[11]

Moreover, a number of courts have approved of multigene genetic testing in mesothelioma and other
cases, including in a February 2023 ruling by the Superior Court of Middlesex County, Massachusetts,
in Gonzalez v. Morse TEC LLC.[12]

And sometimes, courts have approved testing with no restrictions imposed on the number of genes
sequenced, such as in the October 2023 order from the Superior Court for King County, Washington,
in Beckwith v. Genuine Parts Co.[13]

In those cases, most courts have used a typical discovery standard along the lines of "reasonably
likely to lead to the discovery of admissible evidence," and have explicitly declined to weigh the
strength of the genetic causation evidence, as in Gonzales. And in some recent cases, some plaintiffs
firms have withdrawn objections to extensive genetic sequencing.

Thus, a defense motion for genetic testing resulted in a fall 2024 stipulation to sequencing of over
400 genes in Mizer v. Aisin USA Manufacturing Inc., a mesothelioma case in the Superior Court for
Middlesex County, New Jersey.[14] A similar stipulation occurred in Kudenov v. Carborundum
Grinding Wheel Co., a mesothelioma case in the Superior Court for Los Angeles County, California.
[15]

However, some plaintiffs counsel in some venues continue to ardently oppose to extensive genetic
testing. So both plaintiff and defense lawyers need to carefully assess the latest scientific evidence on
genetic causation.

As described below in detail, the Nielsen study is especially important for those cases, because the
analyses provide reproducible, objective statistical evidence that some genetic abnormalities are
sufficient — by themselves — to cause mesotheliomas and other cancers.

Background: The Genetic Basis of Mesothelioma in Human Studies

There have been many steps in the scientific investigation into causal links between asbestos
exposure and mesothelioma. One notable step occurred in 2018, when clinicians and researchers
published data focusing attention on multiple nonasbestos causes of mesothelioma, including other
substances and radiation administered to treat breast and other cancers.[16]

More and more studies, regulators and expert witnesses now acknowledge and report on these
nonasbestos exogenous causes of mesothelioma. Recently, knowledge regarding genetic causes of
mesotheliomas has exploded, due to vastly more whole-genome germline genetic sequencing.

In 2011, researchers published some of the first studies showing that some germline BAP1 mutations
played a role in the development of mesothelioma.[17] In 2021, researchers published a first-of-its-
kind whole-genome sequencing study of 14 people with mesothelioma.[18] Today, far more data is
available.

For example, a global leader in genomic research, UK Biobank, recently provided access to over
500,000 whole genomes matched to medical records. Using that and other resources, including gene
editing tools, a summer 2024 study by U.K. researchers assessed the pathogenicity of 99% of the
thousands of possible BAP1 mutations.[19]

Other studies published over the last several years have shown that mesotheliomas can be caused by
germline mutations in other prominent cancer genes, including BARD1, BRCA1 and BRCA2,[20] as
well as unpredictable combinations of germline and somatic mutations.[21]

Meanwhile, other researchers published studies using data from combined annotation-dependent
depletion scores — which provide objective, reproducible quantitative assessments of the
pathogenicity of germline mutations in BAP1 and other genes, and are highly predictive of cancer.[22]

Finally, in recent years, some courts have ordered whole-exome genetic sequencing from plaintiffs,
and admitted genetic sequencing data arising from physician-ordered genetic testing in their patients.
[23]

The bottom line is that recent human genomic studies have concluded that nonasbestos factors cause
a significant percentage of mesotheliomas. Some sources estimate 20%, while others range as high
as 36%.[24]

How Mouse Studies Shed Light on Mesothelioma

Various groups of scientists have created special mice with genetic changes identical or similar to
those found in some people who develop mesothelioma. Some of these studies involved inserting null
variant mutations into the BAP1 gene.

Most studies looking at these mice focused on what happens when they are exposed to asbestos,
which helps researchers study how mesothelioma develops.

However, one important study by Yuwaraj Kadariya and colleagues in 2016 did something different.
The researchers looked at mice with and without genetically engineered BAP1 mutations, and with
and without asbestos exposure.

This allowed them to see if BAP1 mutations alone could cause mesothelioma, without any asbestos
exposure. They found that two out of 93 mice with BAP1 mutations developed mesothelioma without
exposure to asbestos, while none of the 43 normal mice did.

This suggested BAP1 mutations might cause mesothelioma by themselves. But the small number of
mice made it more difficult to be certain using traditional statistics.

The Nielsen Study: Stronger Evidence From New Statistical Approaches

The Nielsen study used a different statistical approach called Bayesian analysis to look at the same
data. This approach is better suited for studying rare events like spontaneous mesothelioma.

Using this method, they found that when looking just at the mice in Kadariya's study, there was a
70% probability that BAP1 mutations significantly increased mesothelioma risk.

When they included a historical control dataset, containing data from other mouse studies, the
evidence became even stronger. Their analysis showed a 96.7% to 99.5% probability that mice with
BAP1 mutations had higher odds of developing mesothelioma without any asbestos exposure.

The conclusion is clear: BAP1 genetic mutations almost certainly increase the risk of mesothelioma,
even when there is no asbestos exposure.

Implications of This Research for Litigation

The Nielsen study's findings suggest that asbestos exposure is not the only cause of MM in humans.
The data and methods provided by this study make a strong case for the view that, in at least some
cases, MM is caused by pathogenic germline — i.e., inherited — mutations, including null variant
mutations of the BAP1 gene.

These findings also emphasize the importance of genetic testing in diagnosing and treating MM, as
understanding these interactions can significantly enhance personalized medical care.

Notably for mesothelioma litigation stakeholders, the significance of the Nielsen study, as well as
other recent studies, may become more evident through future developments in at least two current
cases in Alameda County, California. Both are cases where a defendant sought multigene genetic
testing, and plaintiffs opposed it, arguing that sequencing should be limited to, at most, the BAP1
gene.

Thus, in Jeanette Combs v. ABB Inc., in Alameda County Superior Court, the judge overseeing
asbestos litigation in Alameda County, Judge Patrick McKinney, issued an order on Feb. 10 that
approved BAP1 genetic testing but rejected multigene testing, after proceedings based on
declarations by defense and plaintiff experts.[25]

Neither declaration was tested through depositions, and neither referred to the Nielsen study or
several other recent studies. The order states:

First, Plaintiffs had previously offered Jeanette Combs's consent [to BAP1 sequencing]. Second
— and independent of her consent — the Court notes that unlike the other identified germline
mutations, there is some evidence that a germline BAP1 mutation can be an independent cause
of mesothelioma unrelated to asbestos exposure. (See, e.g., Chodosh Decl. ¶ 21 ("Consistent
with the interpretation that mutations in these genes are causes of cancer, deletion of BAP1 in
genetically engineered mice has been demonstrated to cause the formation of a variety of
cancers, including mesotheliomas.") Thus, Defendants have a right to discover whether there is
an independent cause of Jeanette Combs's mesothelioma unrelated to any exposure to
asbestos. And to the extent that Jeanette Combs's privacy will be invaded by this genetic test,
the Court finds Defendants' interest in obtaining evidence of independent cause of Jeanette
Combs's mesothelioma is compelling and overrides the minimal invasion of privacy as to
germline mutations of BAP1.

Judge McKinney refused to approve the defense request for testing of 28 genes that are part of a
mesothelioma-specific gene panel offered by the University of Chicago. His order stated the following
conclusions, based on the court's assessment of the quality of the genetic science in the untested
declarations that did not include several recent genomic studies:

With exception to testing for a germline mutation of BAP1, the Court is unpersuaded that good
cause exists to compel Jeanette Combs to submit to genetic testing of the breadth requested
by Contra Costa Electric. With one exception, the Court is likewise skeptical that the proposed
genetic testing is reasonably calculated to lead to the discovery of admissible evidence. (See
Cal. Civ. Proc. Code § 2017.010 (articulating scope of discovery).)

Defendants did not submit sufficient medical evidence that the proposed 20 or 28 germline
mutations independently cause mesothelioma. While some of Dr. Chodosh's statements indicate
that these inherited mutations may independently cause cancers, the Court disagrees that the
submissions show there is "a wealth of evidence [that] now indicates that inherited mutations
can cause mesothelioma." ...

At the hearing, all counsel seemed to understand that this was cutting edge medical research;
and that evidence of a plausible causal link between a germline mutation of benzene, for
instance, and mesothelioma may be discovered in the coming years. Recognizing that these
developments might happen while this case is pending, the Court permits Defendants to renew
their motion to compel genetic testing of germline mutation of one of the identified genes if and
only if a qualified individual can testify that additional cancer research has demonstrated a
plausible causal link between the identified germline mutation and mesothelioma unrelated to
exposure to asbestos.[26]
The second mesothelioma case pending before Judge McKinney is Patsy Stark v. Colgate-Palmolive
Co.[27]

An April motion for genetic testing in that case is notable because: (1) the moving defendant
submitted an expert declaration that presents the Nielsen study and multiple other studies not
presented in Combs; and 2) the defense moved for an order allowing whole-genome sequencing
using a flexible reporting process for the results.

Under that process, the sequencing service would hold the results for all genes, but would release to
the parties the sequencing results for a limited number of genes to be agreed to by the parties or
approved by the court, with results potentially released in batches.

The record in Stark also differs from that in Combs because it includes 2022 deposition testimony by
Dr. Joseph Testa, an expert in genetics who was called by plaintiffs to testify about BAP1 mutations in
multiple Alameda cases between 2014 and 2020, and who published a 2021 study showing the
results of whole-genome sequencing of 14 people with mesothelioma who did not carry a germline
BAP1 mutation.

In testimony prior to 2022, which had been relied on by other judges in Alameda County, Testa
opined that a single germline mutation was not sufficient — by itself — to cause a mesothelioma.[28]
However, his testimony appropriately had changed when he was deposed in 2022 after the
publication of his 2021 article and numerous genomic studies by other researchers.

In his 2022 testimony, Testa acknowledged that genomic abnormalities are sufficient by themselves
to cause some mesotheliomas, and that it is not possible to accurately predict the germline mutations
that may be found in any particular genes in any particular person.[29] Thus, the record in Stark is
notably more complete than the record in Combs, and stakeholders will want to monitor
developments in both proceedings.

The evidence provided by the Nielsen study further cements the need for considering genetic factors
as a cause of MM in a significant number of legal cases, especially when exposure to asbestos is
questionable.

Lawyers representing defendants in asbestos toxic tort litigation can leverage these findings to argue
that an individual plaintiff's MM may have been caused by inherited genetic mutations — including
pathogenic mutations of the BAP1 gene — rather than asbestos exposure.

This perspective could provide pivotal evidence in litigation — potentially leading to different legal
outcomes based on the genetic predispositions of the plaintiffs.

David H. Schwartz, Ph.D., is chief scientific officer at Lumanity Inc.

Kirk T. Hartley is a principal and founder at LSP Group LLC.

Disclosure: Schwartz and Hartley are colleagues of the authors of the Nielsen study
discussed in this article through an alliance known as ToxicoGenomica. Some members of
the ToxicoGenomica alliance have provided consulting and expert witness service to
plaintiffs and defendants in various subsets of mass tort litigation, including mesothelioma
cases.

The opinions expressed are those of the author(s) and do not necessarily reflect the views of their
employer, its clients, or Portfolio Media Inc., or any of its or their respective affiliates. This article is
for general information purposes and is not intended to be and should not be taken as legal advice.

[1] Nielsen, D.M., Hsu, M., Zapata, M., et al., Bayesian analysis of the rate of spontaneous MM among
BAP1 mutant mice in the absence of asbestos exposure, Sci Rep 15, 169
(2025), [Link]
[2] Bowen v. E.I. DuPont de Nemours & Co. , 906 A.2d 787 (Del. 2006).

[3] See Harvey v. Valero Energy Corp., No. 002430, Sept. 10, 2014) (open access at
[Link]
Genetic-Testing-9-10-14); Cacoilo v. The Sherwin-Williams Co., No. CAM-L-5263-11, March 14, 2016
(Camden County Superior Court, N.J.) (open access at
[Link]
Genetic-Testing-W1344323); Howell v. Palmdale Oil Co., #16 – CA -138454 – AE MB (May 9, 2019)
(Palm Beach County, Fla.) (open access at [Link]
Palmdale-Oil-Co-5-9-19-Order-approving-genetic-testing).

[4] Milward v. Acuity Specialty Prods. Group , 639 F.3d 11 (1st Circuit 2011).

[5] Harris v. Mercy Hosp. , 231 Ill. App. 3d 105, 596 N.E.2d 160 (1st Dist. 1992).

[6] Cruz v. Superior Court , 17 Cal. Rptr. 3d 368, 121 Cal. App. 4th 646 (4th Dist. 2004).

[7] Ortega v. U.S. , 2021 U.S. Dist. LEXIS 188969.

[8] See Gary E. Marchant, Genetic Data in Toxic Tort Litigation, The Brief, Winter 2016 (ABA Tort, Trial
& Insurance Section) (available at [Link]
Genetics-inToxic-Tort-Litigation-2016); and Andrew Gendron and Thomas M. Morgan, Incomplete
Penetrance: Whole-Exome Sequencing and Federal Courts, For The Defense, Jan. 2019, at 23
(available at [Link]
m=55594&i=557674&p=24). See also James M. Beck, More on Genetic Testing Orders (Feb. 20,
2020) ([Link]

[9] Bailey v. Autozone Inc., No. 2752-13 (Lawrence Count Circuit Ct., Tenn.) (open access at
[Link]
genetic-testing-with-no-limits-on-genes-to-be-sequenced).

[10] Cole v. Honeywell Int'l., 16 LA- CC-00079-01, March 6, 2019 (Morgan County Circuit Ct., Mo.)
(open access at [Link]
Produce-Tissue-for-genetic-testing-with-no-limits-on-genes).

[11] Holsten v. Amalgamated Sugar Co. LLC, 18 –L -1664, (Madison County Circuit Court, Ill.) (open
access at [Link]
plaintiff-chose-not-to-respond-and-instead-produced-tissue-to-serve-as-the-source-for-DNA).

[12] Gonzalez v. Morse TEC LLC, 21-6584, Feb. 14, 2023 (Superior Court of Middlesex County, MA)
(open access at [Link]
Ruling-on-Genetic-Testing).

[13] Beckwith v. Genuine Parts Co., #21-2-11886-7, Oct. 14, 2022 (King County Sup. Ct.) (open
access at [Link]
for-Genetic-Testing).

[14] Mizer v. Aisin USA Mfg. Inc., Superior Court for Middlesex County, New Jersey (open access at
[Link]
testing-of-over-400-genes).

[15] Kudenov v. Carborundum Grinding Wheel Co., #23STCV28807, July 29, 2024 (open access at
[Link]
listing-81-Genes-With-Results-to-Be-Reported-After-Sequencing-Copy).

[16] Attanoos, R.L., Churg, A., Galateau-Salle, F., Gibbs, A.R., Roggli, V.L., Malignant Mesothelioma
and Its Non-Asbestos Causes, Arch. Pathol. Lab. Med. 2018, 142(6):753-760.

[17] Testa, J.R., Cheung, M., Pei, J., et al., Germline BAP1 mutations predispose to malignant
mesothelioma, Nat. Genet. 2011, 43(10):1022-1025.
[18] Cheung, M., Kadariya, Y., Sementino, E., et al., Novel LRRK2 mutations and other rare, non-
BAP1-related candidate tumor predisposition gene variants in high-risk cancer families with
mesothelioma and other tumors, Hum. Mol. Genet. 2021, 30(18):1750-1761.

[19] Waters, A.J., Brendler-Spaeth, T., Smith, D., et al., Saturation genome editing of BAP1
functionally classifies somatic and germline variants, Nat. Genet. 2024, 56(7):1434-1445.

[20] Novelli, F., Yoshikawa, Y., Vitto, V.A.M., et al., Germline BARD1 variants predispose to
mesothelioma by impairing DNA repair and calcium signaling, Proc. Natl. Acad. Sci. U.S.A. 2024,
121(29):e2405231121.

[21] Mangiante, L., Alcala, N., Sexton-Oates, A., et al., Multiomic analysis of malignant pleural
mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor
heterogeneity, Nat. Genet. 2023, 55(4):607-618.

[22] Pastorino, S., Yoshikawa, Y., Pass, H.I., et al., A Subset of Mesotheliomas With Improved Survival
Occurring in Carriers of BAP1 and Other Germline Mutations, J. Clin. Oncol.; Cheung, M., Kadariya, Y.,
Sementino, E., et al., Novel LRRK2 mutations and other rare, non-BAP1-related candidate tumor
predisposition gene variants in high-risk cancer families with mesothelioma and other tumors, Hum.
Mol. Genet. 2021, 30(18):1750-1761.

[23] Congedo, M.T., West, E.C., Evangelista, J., et al., The genetic susceptibility in the development of
malignant pleural mesothelioma: somatic and germline variants, clinicopathological features and
implication in practical medical/surgical care: a narrative review, J. Thorac. Dis. 2024, 16(1):671-
687.

[24] See Belcaid, L., Bertelsen, B., Wadt, K., et al., New pathogenic germline variants identified in
mesothelioma, Lung Cancer 2023, 179:107172; Andrew Gendron and Thomas M. Morgan,
Incomplete Penetrance: Whole-Exome Sequencing and Federal Courts, For The Defense, Jan. 2019,
at 23 (available at [Link]
m=55594&i=557674&p=24).

[25] Jeanette Combs v. ABB Inc., # 23CV056760 (Alameda County Superior Court).

[26] Subsequently, the moving defendant sought but was summarily denied an interlocutory writ
seeking review of Judge McKinney's ruling on multigene testing, and then filed, but later withdrew,
papers asking the California Supreme Court to review the ruling.

[27] Patsy Stark v. Colgate-Palmolive Co., #22CV018867 (Alameda County Superior Court).

[28] Ortwein v. Certainteed , 2014 Cal. Super. LEXIS 24994, 2014 WL 12911977.

[29] Sotomayor v. Honeywell, #23STCV 01373 (March 19, 2024) (Los Angeles County Superior
Court) (open access at [Link]
19-24-Ruling-granting-BAP1-testing).

All Content © 2003-2025, Portfolio Media, Inc.